Document:

Exhibit 4.4

 

WARRANT AGENT AGREEMENT

 

This Warrant Agent
Agreement (“Warrant Agreement”) is made as of [______________], 2020, by and between PaxMedica, Inc., a
Delaware corporation, with offices at 50 Tice Boulevard, Suite A26, Woodcliff Lake, NJ 07677 (the “Company”),
and Computershare Inc., a Delaware corporation, and its wholly-owned subsidiary Computershare Trust Company N.A. a federally chartered
trust company (collectively, the “Warrant Agent”).

 

WHEREAS, the
Company is engaged in its initial public offering (the “Public Offering”)
of [             ] shares of common stock, par value $0.0001 per
share (the “Common Stock”) and [                  ] warrants (the “Warrants”) entitling its holder to
purchase one share Common Stock for each whole warrant, subject to adjustment as set forth herein (the “Warrant
Shares”) (including the additional shares of Common Stock and Warrants issuable to the underwriter if the
underwriter’s over-allotment option is exercised);

 

WHEREAS, the Company
has filed, with the Securities and Exchange Commission (the “SEC”), a registration statement on Form S-1
(Registration No. 333-239676) (as amended, the “Registration Statement”),
for the registration, under the Securities Act of 1933, as amended (the “Act”), of Common Stock, the Warrants
and the Warrant Shares; and

 

WHEREAS, the Company
desires the Warrant Agent to act on behalf of the Company, and the Warrant Agent is willing to so act, in connection with the issuance,
registration, transfer, exchange, redemption and exercise of the Warrants; and

 

WHEREAS, the Company
desires to provide for the form and provisions of the Warrants, the terms upon which they shall be issued and exercised, and the
respective rights, limitation of rights and immunities of the Company, the Warrant Agent and the holders of the Warrants; and

 

WHEREAS, all acts and
things have been done and performed which are necessary to make the Warrants, when executed on behalf of the Company and countersigned
by or on behalf of the Warrant Agent, as provided herein, the legally valid and binding obligations of the Company, and to authorize
the execution and delivery of this Warrant Agreement.

 

NOW, THEREFORE, in
consideration of the mutual agreements herein contained, the parties hereto agree as follows:

 

1.            Appointment of Warrant Agent. The Company hereby appoints the Warrant Agent to act as agent for the Company for the
Warrants, and the Warrant Agent hereby accepts such appointment and agrees to perform the same in accordance with the express terms
and conditions set forth in this Warrant Agreement.

 

2.            Warrants.

 

2.1          Form of Warrant. Each Warrant shall be: (a) issued in registered form only, (b) in substantially the
form of Exhibit A attached hereto (a “Warrant Certificate”), the provisions of which are incorporated
herein, (c) signed by, or bear the facsimile signature of, the Chairman of the Board of Directors of the Company, the Chief
Executive Officer, the President, the Chief Financial Officer, the Treasurer or Secretary of the Company, and (d) signed manually
or by facsimile signature by the Warrant Agent. In the event the person whose facsimile signature has been placed upon any Warrant
shall have ceased to serve in the capacity in which such person signed the Warrant before such Warrant is issued, it may be issued
with the same effect as if he or she had not ceased to be such at the date of issuance.

 

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2.2          Effect
of Countersignature. Unless and until countersigned by the manual or facsimile signature of the Warrant Agent pursuant to this
Warrant Agreement, a Warrant shall be invalid and of no effect and may not be exercised by the holder thereof.

 

2.3          Registration.

 

2.3.1     Warrant Register. The Warrant Agent shall maintain books (the “Warrant Register”), for the registration
of the original issuance and transfers of the Warrants. Upon the initial issuance of the Warrants, the Warrant Agent shall issue
and register the Warrants in the names of the respective holders thereof in such denominations and otherwise in accordance with
instructions delivered to the Warrant Agent by the Company. Except as provided in this Section 2.3.1, upon the initial
issuance of the Warrants, to the extent the Warrants are DTC eligible as of such date, all of the Warrants shall initially be represented
by one or more Warrant Certificates reflecting book-entry of ownership (each a “Book-Entry Warrant Certificate”),
deposited with the Depository Trust Company (the “Depository”) and registered in the name of Cede &
Co., a nominee of the Depository. Ownership of beneficial interests in the Book-Entry Warrant Certificates shall be shown on, and
the transfer of such ownership shall be effected through, records maintained (i) by the Depository or its nominee for each
Book-Entry Warrant Certificate; (ii) by institutions that have accounts with the Depository (such institution, with respect
to a Warrant in its account, a “Participant”); or (iii) directly on the book-entry records of the Warrant
Agent with respect only to owners of beneficial interests that request such direct registration.

 

If the Warrants are
not DTC-eligible at the issuance date or the Depository subsequently ceases to make its book-entry settlement system available
for the Warrants, the Company may instruct the Warrant Agent regarding making other arrangements for book-entry settlement within
ten (10) Business Days (as defined below) after the Depository ceases to make its book-entry settlement available. In the
event that the Company does not make alternative arrangements for book-entry settlement within ten (10) Business Days, or
the Warrants are not eligible for, or it is no longer necessary to have the Warrants available in, book-entry form, the Warrant
Agent shall provide written instructions, upon receipt of instructions from the Company, to the Depository to deliver to the Warrant
Agent for cancellation each Book-Entry Warrant Certificate, and the Company shall instruct the Warrant Agent to deliver to the
Holder definitive Warrant Certificates in physical form evidencing such Warrants.

 

At the request of any
Holder of Warrants, submitted to the Warrant Agent via the Depositary as the initial Registered Holder as to Book-Entry Warrants,
the Company and Warrant Agent shall deliver to such purchaser definitive Warrant Certificates in physical form, registered in the
name of such purchaser, evidencing the Warrants purchased by such Holder. Such definitive Warrant Certificate shall be dated the
original issue date of the Warrants, shall be executed manually or by facsimile signature by an authorized signatory of the Company,
and countersigned by the manual or facsimile signature of the Warrant Agent, and shall be substantially in the form attached hereto
as Exhibit A.

 

2.3.2      Registered Holder; Beneficial Owners. Prior to due presentment for registration of transfer of any Warrant, the Company
and the Warrant Agent may deem and treat the Person (as defined in the Warrant Certificate) in whose name such Warrant shall be
registered upon the Warrant Register (“Registered Holder”) as the absolute owner of such Warrant and of each
Warrant represented thereby (notwithstanding any notation of ownership or other writing on the Warrant Certificate made by anyone
other than the Company or the Warrant Agent), for the purpose of any exercise thereof, and for all other purposes, and neither
the Company nor the Warrant Agent shall be affected by any notice to the contrary. The term “beneficial owner” shall
mean any Person in whose name ownership of a beneficial interest in the Warrants evidenced by (a) a Book-Entry Warrant Certificate
is recorded in the records maintained by the Depository or its nominee or a Participant or (b) a definitive Warrant Certificate
is recorded in the book-entry records of the Warrant Agent. Any reference herein to the term Holder or Registered Holder shall
include a beneficial owner who has received definitive Warrant Certificates registered in its name.

 

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2.4          Separate
Issuance of Warrants. The Common Stock and the Warrants shall be issued separately and shall be transferable separately immediately
upon issuance. The Common Stock and the Warrants will begin to trade separately on or promptly after the date that is the effective
date of the Registration Statement.

 

2.5          Uncertificated
Warrants. Notwithstanding the foregoing and anything else herein to the contrary, the Warrants may be issued in uncertificated
form if so specified by the Company.

 

2.6          Opinion
of Counsel. The Company shall provide an opinion of counsel to the Warrant Agent prior to the issuance of the Warrants to set
up a reserve of Warrants and related Warrant Shares. The opinion shall state that all Warrants or Warrant Shares, as applicable,
are:

 

(a) registered under
the Securities Act of 1933, as amended, or are exempt from such registration, and all appropriate state securities law filings
have been made with respect to the warrants or shares; and

 

(b)  validly issued,
fully paid and non-assessable.

 

3.            Terms
and Exercise of Warrants.

 

3.1          Warrant Price. Each Warrant shall, when countersigned by the Warrant Agent, entitle the Registered Holder thereof,
subject to the provisions of such Warrant and of this Warrant Agreement, to purchase from the Company the number of shares of Common
Stock stated therein, at the price of $[__] per whole share of Common Stock, subject to the adjustments provided in Section 4
hereof and in the last sentence of this Section 3.1. The term “Warrant Price” as used in this Warrant
Agreement refers to the price per whole share at which Common Stock may be purchased at the time such Warrant is exercised. The
Company, in its sole discretion, may lower the Warrant Price at any time prior to the Expiration Date (as defined below); provided,
that any such reduction remains in effect for no less than ten (10) Business Days and shall be identical in percentage terms
among all of the then outstanding Warrants. The Company shall promptly notify the Warrant Agent of any Warrant Price reduction.

 

3.2          Duration of Warrants. A Warrant may be exercised only during the period (“Exercise Period”) commencing
on the Initial Exercise Date (as defined in the Warrant Certificate) and terminating at 5:00 p.m., New York City time, on September [__],
2025 (“Expiration Date”). Each Warrant not exercised on or before the Expiration Date shall become null and
void, and all rights thereunder and all rights in respect thereof under this Warrant Agreement shall cease at the close of business
on the Expiration Date. The Company may extend the duration of the Warrants by delaying the Expiration Date; provided, however,
that the Company will provide notice of not less than twenty (20) days to the Warrant Agent and Registered Holders of such extension
and that such extension shall be identical in duration among all of the then outstanding Warrants.

 

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3.3          Exercise
of Warrants.

 

3.3.1      Payment. Subject to the provisions of the Warrant and this Warrant Agreement, a Warrant, when countersigned by the
Warrant Agent, may be exercised by the Registered Holder thereof by surrendering at the office of the Warrant Agent, or at the
office of its successor as Warrant Agent, at [ ], (i) the Warrant Certificate evidencing the Warrants to be exercised, or,
in the case of a Book-Entry Warrant Certificate, the Warrants to be exercised (the “Book-Entry Warrants”) shall
be exercised as described herein and Section 2(a) of the Warrant, (ii) the subscription form, as set forth in the
Warrant Certificate (the “Election to Purchase”), properly completed and duly executed by the Registered Holder
on the reverse of the Warrant Certificate or, in the case of a Book-Entry Warrant Certificate, properly delivered by the Participant
in accordance with the Depository’s procedures, and (iii), unless the cashless exercise procedure specified in Section 2(c) of
the Warrant is specified in the applicable Notice of Exercise (a “Cashless Exercise”), payment in full, in lawful
money of the United States, in cash, by wire of same day funds or by certified or bank cashier’s check payable to the order
of the Company, the Warrant Price for such number of Warrant Shares totaling whole shares of Common Stock as to which the Warrant
is exercised and any and all applicable taxes due in connection with the exercise of the Warrant, the exchange of the Warrant for
the Warrant Shares, and the issuance of the Warrant Shares.. Notwithstanding any other provision in this Warrant Agreement, a holder
whose interest in a Book-Entry Warrant is a beneficial interest in a Book-Entry Warrant held through the Depositary (or another
established clearing corporation performing similar functions), shall effect exercises by delivering to the Depositary (or such
other clearing corporation, as applicable) the appropriate instruction form for exercise, complying with the procedures to effect
exercise that are required by Depositary (or such other clearing corporation, as applicable). Upon receipt of an Election to Purchase
for a Cashless Exercise, the Company will promptly calculate and transmit to the Warrant Agent the number of Warrant Shares issuable
in connection with such Cashless Exercise. The Warrant Agent shall have no duty or obligation to investigate or confirm whether
the Company’s determination of the number of Warrant Shares to be issued on such exercise is accurate or correct.

 

3.3.2     Fractional
Shares. Notwithstanding any provision to the contrary contained in this Warrant Agreement, the Company shall not be required
to issue any fractional shares of Common Stock in connection with the exercise of Warrants for Warrant Shares, and in any case
where the Registered Holder would be entitled under the terms of the Warrants to receive a fractional share of Common Stock as
a Warrant Share upon the exercise of such Registered Holder’s Warrants, issue or cause to be issued only the largest whole
number of aggregate Warrant Shares issuable on such exercise (and such remaining fractional shares will be disregarded); provided,
that if more than one Warrant Certificate is presented for exercise at the same time by the same Registered Holder, the number
of Warrant Shares which shall be issuable upon the exercise thereof shall be computed on the basis of the aggregate number of Warrant
Shares issuable on exercise of all such Warrants. The Company shall provide an initial funding of one thousand dollars ($1,000)
for the purpose of issuing cash in lieu of fractional shares. From time to time thereafter, the Warrant Agent may request additional
funding to cover payments for fractional Warrant Shares. The Warrant Agent shall have no obligation to make such payments for fractional
Warrant Shares unless the Company shall have provided the necessary funds to pay in full all amounts due and payable with respect
thereto.

 

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3.3.3     Issuance of Certificates. As soon as practicable after the exercise of any Warrant and the clearance of the funds
in payment of the Warrant Price, the Warrant Agent shall advise the Company and its transfer agent regarding (i) the number
of Warrant Shares issuable upon such exercise in accordance with the terms and conditions of this Warrant Agreement, (ii) the
instructions of each Holder or Participant, as they case may be, with respect to delivery of the Warrant Shares issuable upon such
exercise, and the delivery of definitive Warrant Certificates, as appropriate, evidencing the balance, if any, of the Warrants
remaining after such exercise, (iii) in case of a Book-Entry Warrant Certificate, the notation that shall be made to the records
maintained by the Depository, its nominee for each Book-Entry Warrant Certificate, or a Participant, as appropriate, evidencing
the balance, if any, of the Warrants remaining after such exercise and (iv) such other information as the Company or such
transfer agent and registrar shall reasonably require. Promptly thereafter and within the time period set forth in the Warrants,
the Company shall instruct its transfer agent to issue to the Registered Holder of such Warrant a certificate or certificates representing
the number of full shares of Common Stock to which he, she or it is entitled, registered in such name or names as may be directed
by him, her or it, provided, in lieu of delivering physical certificates representing the Warrant Shares issuable upon exercise,
and provided the Company’s transfer agent is participating in the Depository’s Fast Automated Securities Transfer program,
the Company shall use its commercially reasonable efforts to cause its transfer agent to electronically transmit the Warrant Shares
issuable upon exercise to the Registered Holder by crediting the account of the Participant of record with the Depository or through
its Deposit Withdrawal Agent Commission system. If such Warrant shall not have been exercised or surrendered in full, a new countersigned
Warrant Certificate for the number of shares as to which such Warrant shall not have been exercised or surrendered, or, in case
of a Book-Entry Warrant Certificate, a notation shall be made to the records maintained by the Depository or nominee for each Book-Entry
Warrant Certificate, as appropriate, evidencing the balance, if any, of the Warrants remaining after such exercise. Notwithstanding
the foregoing, the Company shall not be obligated to deliver any securities pursuant to the exercise of a Warrant unless (a) a
registration statement under the Act with respect to the Common Stock issuable upon exercise of such Warrants is effective and
a current prospectus relating to the shares of Common Stock issuable upon exercise of the Warrants is available for delivery to
the Registered Holder of the Warrant or (b) in the opinion of counsel to the Company, the exercise of the Warrants is exempt
from the registration requirements of the Act and such securities are qualified for sale or exempt from qualification under applicable
securities laws of the states or other jurisdictions in which the Registered Holder resides. Until otherwise advised in writing
by the Company, the Warrant Agent shall always be entitled to assume that either clause (a) or clause (b) is in effect
and shall incur no liability in making such assumption. Warrants may not be exercised by, or securities issued to, any Registered
Holder in any state in which such exercise or issuance would be unlawful. In the event a such exercise would be unlawful with respect
to a Registered Holder in any state, the Registered Holder shall not be entitled to exercise such Warrants and such Warrants may
have no value and expire worthless. In no event will the Company be obligated to pay such Registered Holder any cash consideration
upon exercise or otherwise “net cash settle” the Warrant.

 

3.3.4     Valid
Issuance. The validity of any exercise of Warrants will be determined by the Company in its reasonable discretion. The Warrant
Agent shall notify a holder of any purported invalidity of any exercise of Warrants. All shares of Common Stock issued upon the
proper exercise or surrender of a Warrant in conformity with this Warrant Agreement shall be validly issued, fully paid and nonassessable.

 

3.3.5     Date of Issuance. Each Person in whose name any shares of Common Stock is issued shall, for all purposes, be deemed
to have become the holder of record of such shares on the date on which the Warrant was surrendered and payment of the Warrant
Price was made, irrespective of the date of delivery of such certificate, except that, if the date of such surrender and payment
is a date when the stock transfer books of the Company are closed, such Person shall be deemed to have become the holder of such
shares at the close of business on the next succeeding date on which the stock transfer books are open (the “Exercise
Date”). If any of (i) the Warrant Certificate or the Book-Entry Warrants, (ii) the Election to Purchase, or
(iii) the Warrant Price therefor, is received by the Warrant Agent after 5:00 P.M., New York time, on the specified Exercise
Date, the Warrants will be deemed to be received and exercised on the Business Day next succeeding the Exercise Date, subject to
clearance of the funds. If the date specified as the Exercise Date is not a Business Day, the Warrants will be deemed to be received
and exercised on the next succeeding day that is a Business Day, subject to clearance of the funds. If the Warrants are received
or deemed to be received after the Expiration Date, the exercise thereof will be null and void and any funds delivered to the Warrant
Agent will be returned to the Registered Holder as soon as practicable.

 

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3.3.6      Cost
Basis Information.

 

(a)         In
the event of a cash exercise, the Company hereby instructs the Warrant Agent to record cost basis for newly issued shares in a
manner to be subsequently communicated by the Company in writing to the Warrant Agent

 

(b)         In
the event of a Cashless Exercise, the Company shall provide cost basis for shares issued pursuant to a cashless exercise at the
time the Company confirms the number of Warrant Shares issuable in connection with the cashless exercise to the Warrant Agent pursuant
to Section 3.3.1 hereof.

 

4.            Adjustments;
Rights. The Warrant Shares and Warrant Price shall be subject to adjustment as provided for in the Warrant Certificate, and
the rights of Warrant holders as provided for in the Warrant Certificate are incorporated herein by reference and shall be adhered
to by the Company and the Warrant Agent. The Company hereby agrees that it will provide the Warrant Agent with reasonable notice
of any adjustment events. The Company further agrees that it will provide to the Warrant Agent with any new or amended exercise
terms. Whenever the Warrant Shares or Warrant Price or the number of shares of Common Stock issuable upon the exercise of each
Warrant is adjusted, the Company shall (a) promptly prepare a certificate setting forth the Warrant Price of each Warrant
as so adjusted, and a brief statement of the facts accounting for such adjustment, (b) promptly file with the Warrant Agent
and with each transfer agent for the Common Stock a copy of such certificate and (c) instruct the Warrant Agent to send a
brief summary thereof to each Holder of a Warrant Certificate. The Warrant Agent shall be fully protected in relying on any such
certificate and on any adjustment or statement therein contained and shall have no duty or liability with respect to, and shall
not be deemed to have knowledge of any such adjustment or any such event unless and until it shall have received such certificate.

 

5.            Transfer
and Exchange of Warrants.

 

5.1          Transfer
of Warrants. The Warrants may be transferred or exchanged separately from shares of Common Stock.

 

5.2          Registration of Transfer. The Warrant Agent shall register the transfer, from time to time, of any outstanding Warrant
into the Warrant Register, upon surrender of such Warrant for transfer, properly endorsed with signatures properly guaranteed and
accompanied by appropriate instructions for transfer, or properly noticed by the Depositary as contemplated by Section 5.3.
Upon any such transfer, a new Warrant, representing an equal aggregate number of Warrants shall be issued and the old Warrant shall
be cancelled by the Warrant Agent. The Warrants so cancelled shall be delivered by the Warrant Agent to the Company from time to
time upon the Company’s request. A party requesting transfer of Warrants must provide any evidence of authority that may
be required by the Warrant Agent, including but not limited to, a signature guarantee from an eligible guarantor institution participating
in a signature guarantee program approved by the Securities Transfer Association.

 

5.3          Procedure for Surrender of Warrants. Warrants may be surrendered to the Warrant Agent, together with a written request
for exchange or transfer reasonably acceptable to Warrant Agent, duly executed by the registered holder thereof, or by a duly authorized
attorney, and, thereupon, the Warrant Agent shall issue in exchange therefor one or more new Warrants as requested by the Registered
Holder of the Warrants so surrendered, representing an equal aggregate number of Warrants; provided, however, that, except as otherwise
provided herein or in any Book-Entry Warrant Certificate, each Book-Entry Warrant Certificate may be transferred only in whole
and only to the Depository, to another nominee of the Depository, to a successor depository, or to a nominee of a successor depository;
provided further, that in the event a Warrant surrendered for transfer bears a restrictive legend, the Warrant Agent shall not
cancel such Warrant and shall issue new Warrants in exchange therefor until the Warrant Agent has received an opinion of counsel
for the Company stating that such transfer may be made and indicating whether the new Warrants must also bear a restrictive legend.
Notwithstanding anything else in this Section 5.3, in case of a Book-Entry Warrant, the holder or Participant shall notify
the Depositary in accordance with the Depository’s procedures of a requested transfer and the Depositary shall provide notice
to an account of the Warrant Agent at the Depository designated for such purpose in writing by the Warrant Agent to the Depository
from time to time, of a transfer to be recorded in the records maintained by the Depository, its nominee for each Book-Entry Warrant
Certificate, or a Participant, as appropriate, evidencing the balance, if any, of the Warrants remaining after such transfer and
the new name in which the transferred Book Entry Warrants are to be held.

 

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5.4          Fractional Warrants. The Warrant Agent shall not be required to effect any registration of transfer or exchange which
will result in the issuance of a Warrant Certificate or a Book-Entry Warrant Certificate for a fraction of a Warrant.

 

5.5          Warrant Execution and Countersignature. The Warrant Agent is hereby authorized to countersign and to deliver, in
accordance with the terms of this Warrant Agreement, the Warrants required to be issued pursuant to the provisions of this Section 5,
and the Company, whenever required by the Warrant Agent, will supply the Warrant Agent with Warrants duly executed on behalf of
the Company for such purpose.

 

6.            Other
Provisions Relating to Rights of Registered Holders of Warrants.

 

6.1          No Rights as Stockholder. A Warrant does not entitle the Registered Holder thereof to any of the rights of a stockholder
of the Company, including, without limitation, the right to receive dividends, or other distributions, exercise any preemptive
rights to vote or to consent or to receive notice as stockholders in respect of the meetings of stockholders or the election of
directors of the Company or any other matter.

 

6.2          Lost, Stolen Mutilated or Destroyed Warrants. If any Warrant is lost, stolen, mutilated or destroyed, the Company
and the Warrant Agent may, absent notice to Warrant Agent that such certificates have been acquired by a bona fide purchaser, on
such terms as to indemnity or otherwise as they may in their discretion impose (which terms shall in all cases include posting
of a lost security bond by or on behalf of the Registered Holder, and in the case of a mutilated Warrant, include the surrender
thereof), issue a new Warrant of like denomination, tenor and date as the Warrant so lost, stolen, mutilated or destroyed. Any
such new Warrant shall constitute a substitute contractual obligation of the Company, whether or not the allegedly lost, stolen,
mutilated or destroyed Warrant shall be at any time enforceable by anyone.

 

6.3          Reservation of Common Stock. The Company shall at all times reserve and keep available a number of its authorized
but unissued shares of Common Stock that will be sufficient to permit the exercise in full of all outstanding Warrants issued pursuant
to this Warrant Agreement.

 

6.4          Registration of Common Stock. The Company agrees to use its commercially reasonable efforts to maintain the effectiveness
of the Registration Statement until the expiration of the Warrants in accordance with the provisions of this Warrant Agreement;
provided, however, that the Company shall not have penalties for failure to deliver Common Stock if a registration statement is
not effective or a current prospectus is not on file with the SEC at the time of exercise by the Registered Holder. In addition,
to the extent not completed at the time of the initial issuance of the Warrants, the Company agrees to use its reasonable efforts
to register such securities under the blue sky laws of the states of residence of the exercising Registered Holders to the extent
an exemption under the Act is not available for the exercise of the Warrants. In no event will the Registered Holder of a Warrant
be entitled to receive a net-cash settlement or shares of Common Stock or other consideration as of result of the Company’s
non-compliance with this Section 6.4. The provisions of this Section 6.4 may not be modified, amended or
deleted without the prior written consent of The Benchmark Company, LLC, the lead underwriter of the Public Offering (the “Underwriter”).

 

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7.            Concerning
the Warrant Agent and Other Matters.

 

7.1          Payment of Taxes. The Company will, from time to time, promptly pay all taxes and charges that may be imposed upon
the Company or the Warrant Agent in respect of the issuance or delivery of shares of Common Stock upon the exercise of Warrants,
but neither the Company nor the Warrant Agent shall be obligated to pay any transfer taxes in respect of the Warrants or such shares.
The Warrant Agent shall not register any transfer or issue or deliver any Warrant Certificate(s) or Warrant Shares unless
or until the Persons requesting the registration or issuance shall have paid to the Warrant Agent for the account of the Company
the amount of such tax, if any, or shall have established to the reasonable satisfaction of the Company and the Warrant Agent that
such tax, if any, has been paid.

 

7.2          Resignation,
Consolidation, or Merger of Warrant Agent.

 

7.2.1     Appointment of Successor Warrant Agent. The Warrant Agent, or any successor to it hereafter appointed, may resign
its duties and be discharged from all further duties and liabilities hereunder after giving thirty (30) days’ notice in writing
to the Company. If the office of the Warrant Agent becomes vacant by resignation or incapacity to act or otherwise, the Company
shall appoint, in writing, a successor Warrant Agent in place of the Warrant Agent. If the Company shall fail to make such appointment
within a period of thirty (30) days after it has been notified in writing of such resignation or incapacity by the Warrant Agent
or by the Registered Holder of the Warrant (who shall, with such notice, submit his, her or its Warrant for inspection by the Company),
then the Registered Holder of any Warrant may apply to the Supreme Court of the State of New York for the County of New York for
the appointment of a successor Warrant Agent. Any successor Warrant Agent, whether appointed by the Company or by such court, shall
be an entity authorized under applicable laws to exercise the powers of a transfer agent and subject to supervision or examination
by federal or state authorities. After appointment, any successor Warrant Agent shall be vested with all the authority, powers,
rights, immunities, duties and obligations of its predecessor Warrant Agent with like effect as if originally named as Warrant
Agent hereunder, without any further act or deed; but, if for any reason it becomes necessary or appropriate, the predecessor Warrant
Agent shall execute and deliver, at the expense of the Company, an instrument transferring to such successor Warrant Agent all
the authority, powers, and rights of such predecessor Warrant Agent hereunder; and, upon request of any successor Warrant Agent,
the Company shall make, execute, acknowledge, and deliver any and all instruments in writing for more fully and effectually vesting
in and confirming to such successor Warrant Agent all such authority, powers, rights, immunities, duties and obligations.

 

7.2.2     Notice of Successor Warrant Agent. In the event a successor Warrant Agent shall be appointed, the Company shall give
notice thereof to the predecessor Warrant Agent and the transfer agent for the Common Stock not later than thirty (30) days before
the effective date of any such appointment.

 

7.2.3     Merger or Consolidation of Warrant Agent. Any Person into which the Warrant Agent may be merged or with which it
may be consolidated or any Person resulting from any merger or consolidation to which the Warrant Agent shall be a party shall
be the successor Warrant Agent under this Warrant Agreement without any further act on the part of the Company or the Warrant Agent.

 

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7.2.4     Confidentiality. The Warrant Agent and the Company agree that all books, records, information and data pertaining
to the business of the other party, including inter alia, personal, non-public Holder information, which are exchanged or received
pursuant to the negotiation or the carrying out of this Warrant Agreement shall remain confidential, and shall not be voluntarily
disclosed to any other Person, except as may be required by law, including, without limitation, pursuant to subpoenas from state
or federal government authorities.

 

7.3          Fees
and Expenses of Warrant Agent.

 

7.3.1     Remuneration. The Company agrees to pay the Warrant Agent reasonable remuneration for its services as Warrant Agent
hereunder as set forth on Exhibit B hereto and will reimburse the Warrant Agent upon demand for all expenditures that
the Warrant Agent may reasonably incur in the execution of its duties hereunder.

 

7.3.2     Further Assurances. The Company agrees to perform, execute, acknowledge and deliver, or cause to be performed, executed,
acknowledged and delivered, all such further and other acts, instruments and assurances as may reasonably be required by the Warrant
Agent for the carrying out or performing of the provisions of this Warrant Agreement.

 

7.4          Liability
of Warrant Agent.

 

7.4.1     Reliance on Company Statement. Whenever, in the performance of its duties under this Warrant Agreement, the Warrant
Agent shall deem it necessary or desirable that any fact or matter be proved or established by the Company prior to taking or suffering
any action hereunder, such fact or matter (unless other evidence in respect thereof be herein specifically prescribed) may be deemed
to be conclusively proved and established by a statement signed by the Chief Executive Officer, Chief Financial Officer or Chairman
of the Board of the Company and delivered to the Warrant Agent. The Warrant Agent may rely upon, and be held harmless for such
reliance, such statement for any action taken or suffered or omitted to be taken by it in the absence of bad faith pursuant to
the provisions of this Warrant Agreement, and shall not be held liable in connection with any delay in receiving such statement.

 

7.4.2     Indemnity. The Warrant Agent shall be liable hereunder only for its own gross negligence, willful misconduct or bad
faith (each as determined by a final judgment of a court of competent jurisdiction). The Company covenants and agrees to indemnify
the Warrant Agent and hold it harmless against any and all liabilities, including judgments, losses, damages, costs, expenses,
and reasonable counsel fees, which may be paid, incurred or suffered by or to which it may become subject, arising from or out
of, directly or indirectly, any claims or liability resulting from its actions as Warrant Agent pursuant hereto; provided, that
such covenant and agreement does not extend to, and the Warrant Agent shall not be indemnified with respect to, such costs, expenses,
losses and damages incurred or suffered by the Warrant Agent as a result of, or arising out of, its gross negligence, willful misconduct
or bad faith (each as determined by a final judgment of a court of competent jurisdiction).

 

7.4.3     Exclusions.
The Warrant Agent shall have no responsibility with respect to the validity of this Warrant Agreement or with respect to the
validity or execution of any Warrant (except its countersignature thereof); nor shall it be responsible for any breach by the
Company of any covenant or condition contained in this Warrant Agreement or in any Warrant; nor shall it be responsible to make
any adjustments required under the provisions of Section 4 hereof or responsible for the manner, method or amount
of any such adjustment or the ascertaining of the existence of facts that would require any such adjustment; nor shall it, by
any act hereunder, be deemed to make any representation or warranty as to the authorization or reservation of any shares of Common
Stock to be issued pursuant to this Warrant Agreement or any Warrant or as to whether any shares of Common Stock will when issued
be valid and fully paid and nonassessable.

 

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7.4.4     Instructions.
From time to time, the Company may provide the Warrant Agent with instructions concerning the services performed by the Warrant
Agent hereunder. In addition, at any time the Warrant Agent may apply to any officer of Company for instruction, and may consult
with legal counsel for the Warrant Agent or the Company with respect to any matter arising in connection with the services to be
performed by the Warrant Agent under this Warrant Agreement. Warrant Agent and its agents and subcontractors shall not be liable
and shall be indemnified by Company for any action taken, suffered or omitted to be taken by Warrant Agent in reliance upon any
Company instructions or upon the advice or opinion of such counsel. Warrant Agent shall not be held to have notice of any change
of authority of any Person, until receipt of written notice thereof from Company.

 

7.4.5     Rights
and Duties of Warrant Agent. (a)  The Warrant Agent may consult with legal counsel (who may be
legal counsel for the Company), and the advice or opinion of such counsel shall be full and complete authorization and protection
to the Warrant Agent as to any action taken, suffered or omitted by it in accordance with such advice or opinion.

 

(b)        The
Warrant Agent shall not be liable for or by reason of any of the statements of fact or recitals contained in this Warrant Agreement
or in the Warrant Certificates (except its countersignature thereof) or be required to verify the same, and all such statements
and recitals are and shall be deemed to have been made by the Company only.

 

(c)        The
Warrant Agent shall not be required to take notice or be deemed to have notice of any event or condition hereunder, including any
event or condition that may require action by the Warrant Agent, unless the Warrant Agent shall be specifically notified in writing
of such event or condition by the Company, and all notices or other instruments required by this Warrant Agreement to be delivered
to the Warrant Agent must, in order to be effective, be received by the Warrant Agent as specified in Section 8.2 hereof,
and in the absence of such notice so delivered, the Warrant Agent may conclusively assume no such event or condition exists.

 

(d)         The
Warrant Agent and any stockholder, director, officer or employee of the Warrant Agent may buy, sell or deal in any of the Warrants
or other securities of the Company or become pecuniarily interested in any transaction in which the Company may be interested,
or contract with or lend money to the Company or otherwise act as fully and freely as though it were not Warrant Agent under this
Warrant Agreement. Nothing herein shall preclude the Warrant Agent from acting in any other capacity for the Company or for any
other legal entity.

 

(e)        The
Warrant Agent may execute and exercise any of the rights or powers hereby vested in it or perform any duty hereunder either itself
or by or through its attorney or agents, and the Warrant Agent shall not be answerable or accountable for any act, default, neglect
or misconduct of any such attorney or agents or for any loss to the Company resulting from any such act, default, neglect or misconduct,
absent gross negligence, bad faith or willful misconduct (each as determined by a final judgment of a court of competent jurisdiction)
in the selection and continued employment thereof.

 

(f)         The
Warrant Agent may rely on and shall be held harmless and protected and shall incur no liability for or in respect of any action
taken, suffered or omitted to be taken by it in reliance upon any certificate, statement, instrument, opinion, notice, letter,
facsimile transmission or other document, or any security delivered to it, and believed by it to be genuine and to have been made
or signed by the proper party or parties, or upon any written or oral instructions or statements from the Company with respect
to any matter relating to its acting as Warrant Agent hereunder.

 

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(g)        The
Warrant Agent shall not be obligated to expend or risk its own funds or to take any action that it believes would expose or subject
it to expense or liability or to a risk of incurring expense or liability, unless it has been furnished with assurances of repayment
or indemnity satisfactory to it.

 

(h)        The
Warrant Agent shall not be liable or responsible for any failure of the Company to comply with any of its obligations relating
to any registration statement filed with the SEC or this Warrant Agreement, including without limitation obligations under applicable
regulation or law.

 

(i)         The
Warrant Agent shall not be accountable or under any duty or responsibility for the use by the Company of any Warrants authenticated
by the Warrant Agent and delivered by it to the Company pursuant to this Warrant Agreement or for the application by the Company
of the proceeds of the issue and sale, or exercise, of the Warrants.

 

(j)         The
Warrant Agent shall act hereunder solely as agent for the Company, and its duties shall be determined solely by the express provisions
hereof (and no duties or obligations shall be inferred or implied). The Warrant Agent shall not assume any obligations or relationship
of agency or trust with any of the owners or holders of the Warrants.

 

(k)        The
Warrant Agent may rely on and be fully authorized and protected in acting or failing to act upon (a) any guaranty of signature
by an “eligible guarantor institution” that is a member or participant in the Securities Transfer Agents Medallion
Program or other comparable “signature guarantee program” or insurance program in addition to, or in substitution for,
the foregoing; or (b) any law, act, regulation or any interpretation of the same even though such law, act, or regulation
may thereafter have been altered, changed, amended or repealed.

 

(l)         In
the event the Warrant Agent believes any ambiguity or uncertainty exists hereunder or in any notice, instruction, direction, request
or other communication, paper or document received by the Warrant Agent hereunder, the Warrant Agent, may, in its sole discretion,
refrain from taking any action, and shall be fully protected and shall not be liable in any way to Company, the holder of any Warrant
Certificate or Book-Entry Warrant Certificate or any other Person for refraining from taking such action, unless the Warrant Agent
receives written instructions signed by the Company which eliminates such ambiguity or uncertainty to the satisfaction of Warrant
Agent.

 

(m)       Notwithstanding
anything contained herein to the contrary, the Warrant Agent’s aggregate liability during any term of this Warrant Agreement
with respect to, arising from, or arising in connection with this Warrant Agreement, or from all services provided or omitted to
be provided under this Warrant Agreement, whether in contract, or in tort, or otherwise, is limited to, and shall not exceed, the
amounts paid hereunder by the Company to the Warrant Agent as fees and charges, but not including reimbursable expenses, during
the twelve (12) months immediately preceding the event for which recovery from the Warrant Agent is being sought. Neither party to
this Warrant Agreement shall be liable to the other party for any consequential, indirect, special, punitive or incidental damages
under any provisions of this Warrant Agreement or for any consequential, indirect, punitive, special or incidental damages arising
out of any act or failure to act hereunder even if that party has been advised of or has foreseen the possibility or likelihood
of such damages.

 

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7.5         Acceptance of Agency. The Warrant Agent hereby accepts the agency established by this Warrant Agreement and agrees
to perform the same upon the express terms and conditions herein set forth and, among other things, shall account promptly to the
Company with respect to Warrants exercised and concurrently account for, and forward to the Company all moneys received for warrant
exercises in a given month by the 5th business day of the following month by wire transfer to an account designated by the Company.

 

7.6          Survival. The Warrant Agent’s indemnities, immunities and protections provided by this Section 7 shall
survive the resignation or discharge of the Warrant Agent or the termination of this Warrant Agreement.

 

8.            Miscellaneous
Provisions.

 

8.1          Successors. All the covenants and provisions of this Warrant Agreement by or for the benefit of the Company or the
Warrant Agent shall bind and inure to the benefit of their respective successors and assigns.

 

8.2         Notices. Any notice, statement or demand authorized by this Warrant Agreement to be given or made by the Warrant
Agent or by the Registered Holder of any Warrant to or on the Company shall be delivered by hand or sent by registered or certified
mail or overnight courier service, addressed (until another address is filed in writing by the Company with the Warrant Agent)
as follows:

 

PaxMedica, Inc. 

50 Tice Boulevard 

Suite A26 

Woodcliff Lake, NJ 07677 

Attention: Chief Financial Officer

 

Any notice, statement or demand authorized
by this Warrant Agreement to be given or made by the Registered Holder of any Warrant or by the Company to or on the Warrant Agent
shall be delivered by hand or sent by registered or certified mail or overnight courier service, addressed (until another address
is filed in writing by the Warrant Agent with the Company), as follows:

 

Computershare Inc. 

Computershare Trust Company, N.A. 

150 Royall Street 

Canton, MA 02021 

Attention: Client Services

 

Any notice, sent by the Warrant Agent pursuant
to this Warrant Agreement shall be effective when sent. Any other notice, sent pursuant to this Warrant Agreement shall be effective,
if delivered by hand, upon receipt thereof by the party to whom it is addressed, if sent by overnight courier, on the next Business
Day of the delivery to the courier, and if sent by registered or certified mail on the third day after registration or certification
thereof.

 

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8.3          Applicable Law. The validity, interpretation, and performance of this Warrant Agreement and of the Warrants shall
be governed in all respects by the laws of the State of New York, without giving effect to conflict of laws. The Company and the
Warrant Agent hereby agree that any action, proceeding or claim against either of them arising out of or relating in any way to
this Warrant Agreement shall be brought and enforced in the courts of the State of New York or the United States District Court
for the Southern District of New York, and irrevocably submits to such jurisdiction, which jurisdiction shall be exclusive. The
Company and the Warrant Agent hereby waive any objection to such exclusive jurisdiction and that such courts represent an inconvenient
forum. Any such process or summons to be served upon the Company or the Warrant Agent may be served by transmitting a copy thereof
by registered or certified mail, return receipt requested, postage prepaid, addressed to it at the address set forth in Section 8.2
hereof. Such mailing shall be deemed personal service and shall be legal and binding upon the Company and the Warrant Agent in
any action, proceeding or claim.

 

8.4          Persons Having Rights under this Warrant Agreement. Nothing in this Warrant Agreement expressed and nothing that
may be implied from any of the provisions hereof is intended, or shall be construed, to confer upon, or give to, any Person other
than the parties hereto and the Registered Holders of the Warrants and, for the purposes of Sections 6.4, 8.2 and 8.8
hereof, the Underwriter, any right, remedy, or claim under or by reason of this Warrant Agreement or of any covenant, condition,
stipulation, promise, or agreement hereof. The Underwriter shall be deemed to be a third-party beneficiary of this Warrant Agreement
with respect to Sections 6.4, 8.2 and 8.8 hereof. All covenants, conditions, stipulations, promises, and agreements
contained in this Warrant Agreement shall be for the sole and exclusive benefit of the parties hereto (and the Underwriter with
respect to the Sections 6.4, 8.2 and 8.8 hereof) and its successors and assigns and of the Registered Holders of
the Warrants.

 

8.5          Examination of the Warrant Agreement. A copy of this Warrant Agreement shall be available at all reasonable times
at the office of the Warrant Agent for inspection by the Registered Holder of any Warrant. The Warrant Agent may require any such
Registered Holder to submit his, her or its Warrant for inspection.

 

8.6          Counterparts; Facsimile Signatures. This Warrant Agreement may be executed in any number of counterparts, and each
of such counterparts shall, for all purposes, be deemed to be an original, and all such counterparts shall together constitute
one and the same instrument. Facsimile or electronic signatures shall constitute original signatures for all purposes of this Warrant
Agreement and shall have the same authority, effect and enforceability as an original signature.

 

8.7          Effect
of Headings. The section headings herein are for convenience only and are not part of this Warrant Agreement and shall not
affect the interpretation thereof

 

8.8         Amendments. This Warrant Agreement and any Warrant certificate may be amended by the parties hereto by executing
a supplemental warrant agreement (a “Supplemental Agreement”), without the consent of any of the Warrant Holders,
for the purpose of (i) curing any ambiguity, or curing, correcting or supplementing any defective provision contained herein,
or making any other provisions with respect to matters or questions arising under this Warrant Agreement that is not inconsistent
with the provisions of this Warrant Agreement or the Warrant certificates, (ii) evidencing the succession of another entity
to the Company and the assumption by any such successor of the covenants of the Company contained in this Warrant Agreement and
the Warrants, (iii) evidencing and providing for the acceptance of appointment by a successor Warrant Agent with respect to
the Warrants, (iv) adding to the covenants of the Company for the benefit of the Registered Holders or surrendering any right
or power conferred upon the Company under this Warrant Agreement, or (viii) amending this Warrant Agreement and the Warrants
in any manner that the Company may deem to be necessary or desirable and that will not adversely affect the interests of the Registered
Holders in any material respect. All other modifications or amendments, including any amendment to increase the Warrant Price or
shorten the Exercise Period, shall require the written consent of the Registered Holders representing at least of 50.1% of the
Warrant Shares issuable under the Warrants then outstanding. Notwithstanding the foregoing, the Company may lower the Warrant Price
or extend the duration of the Exercise Period in accordance with Sections 3.1 and 3.2, respectively, without such
consent. As a condition precedent to the Warrant Agent’s execution of any amendment, the Company shall deliver to the Warrant
Agent a certificate from a duly authorized officer of the Company that states that the proposed amendment is in compliance with
the terms of this Section 8.8.

 

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8.9          Severability. This Warrant Agreement shall be deemed severable, and the invalidity or unenforceability of any term
or provision hereof shall not affect the validity or enforceability of this Warrant Agreement or of any other term or provision
hereof. Furthermore, in lieu of any such invalid or unenforceable term or provision, the parties hereto intend that there shall
be added as a part of this Warrant Agreement a provision as similar in terms to such invalid or unenforceable provision as may
be possible and be valid and enforceable.

 

8.10        Business
Day. For purposes of this Warrant Agreement, a “Business Day” is any day other than a Saturday, Sunday or
a day on which commercial banks in The City of New York are authorized or required by law to remain closed; provided, however,
for clarification, commercial banks shall not be deemed to be authorized or required by law to remain closed due to “stay
at home”, “shelter-in-place”, “non-essential employee” or any other similar orders or restrictions
or the closure of any physical branch locations at the direction of any governmental authority so long as the electronic funds
transfer systems (including for wire transfers) of commercial banks in The City of New York generally are open for use by customers
on such day.

 

8.11        Bank
Accounts. All funds received by Computershare Inc. under this Warrant Agreement that are to be distributed or applied by Computershare
Inc. in the performance of its services hereunder (the “Funds”) shall be held by Computershare Inc. as agent
for the Company and deposited in one or more bank accounts to be maintained by Computershare Inc. in its name as agent for the
Company.  Until paid pursuant to the terms of this Warrant Agreement, Computershare will hold the Funds through such accounts
in: deposit accounts of commercial banks with Tier 1 capital exceeding $1 billion or with an average rating above investment grade
by S&P (LT Local Issuer Credit Rating), Moody’s (Long Term Rating) and Fitch Ratings, Inc. (LT Issuer Default Rating)
(each as reported by Bloomberg Finance L.P.).  Computershare Inc. shall have no responsibility or liability for any diminution
of the Funds that may result from any deposit made by Computershare Inc. in accordance with this paragraph, including any
losses resulting from a default by any bank, financial institution or other third party.  Computershare Inc. may from time
to time receive interest, dividends or other earnings in connection with such deposits.  Computershare Inc. shall not be
obligated to pay such interest, dividends or earnings to the Company, any holder of Warrants or any other party.

 

8.12        Force
Majeure. Notwithstanding anything to the contrary contained herein, the Warrant Agent will not be liable for any delays or
failures in performance resulting from acts beyond its reasonable control including, without limitation, acts of God, pandemics,
epidemics, terrorist acts, shortage of supply, breakdowns or malfunctions, interruptions or malfunction of computer facilities,
or loss of data due to power failures or mechanical difficulties with information storage or retrieval systems, labor difficulties,
war, or civil unrest.

 

[SIGNATURE PAGE FOLLOWS]

 

    14

     

    

 

IN WITNESS
WHEREOF, this Warrant
Agreement has been duly
executed by the patties
hereto as of the day
and year first above written.

 

	 	PAXMEDICA, Inc.
	 	 
	 	By:	 
	 	 	Name:	               
	 	 	Title:	 

 

	 	COMPUTERSHARE TRUST COMPANY, N.A and
	 	COMPUTERSHARE INC.
	 	 
	 	By:	
	 	 	Name:	                  
	 	 	Title:	 

 

    

     

    

 

EXHIBIT A

 

Form of Warrant Certificate

 

[attached hereto]

 

    

     

    

 

EXHIBIT B

 

Warrant Agent Fees

 

[to be provided]EX-4.1

 Exhibit 4.1 

Execution Version 

MEDTRONIC GLOBAL HOLDINGS S.C.A. 

as Issuer, 
 MEDTRONIC
PUBLIC LIMITED COMPANY 
 and MEDTRONIC, INC. 

as Guarantors, 
 WELLS
FARGO BANK, NATIONAL ASSOCIATION, 
 as Trustee, 

and 
 ELAVON FINANCIAL
SERVICES DAC, 
 as Paying Agent 

FOURTH SUPPLEMENTAL INDENTURE 

DATED AS OF SEPTEMBER 29, 2020 

TO INDENTURE 
 DATED AS
OF MARCH 28, 2017 
 Relating to 

€1,250,000,000 0.000% Senior Notes due 2023 

€1,000,000,000 0.000% Senior Notes due 2025 

€1,000,000,000 0.375% Senior Notes due 2028 

€1,000,000,000 0.750% Senior Notes due 2032 

€1,000,000,000 1.375% Senior Notes due 2040 

€1,000,000,000 1.625% Senior Notes due 2050 

 FOURTH SUPPLEMENTAL INDENTURE 

FOURTH SUPPLEMENTAL INDENTURE, dated as of September 29, 2020 (the “Supplemental Indenture”), to the Base Indenture
(defined below) among MEDTRONIC GLOBAL HOLDINGS S.C.A., a corporate partnership limited by shares (société en commandite par actions) incorporated and existing under the laws of the Grand Duchy of Luxembourg, having its
registered office at Espace Monterey, 40, Avenue Monterey, Ground Floor, L2163 Luxembourg, Grand Duchy of Luxembourg and registered with the Luxembourg Trade and Companies Register under number B191129 (the “Company”), MEDTRONIC
PUBLIC LIMITED COMPANY, a public limited company incorporated under the laws of Ireland (“Parent”), MEDTRONIC, INC., a Minnesota corporation (“Medtronic, Inc.” and, together with Parent, the
“Guarantors”), Wells Fargo Bank, National Association, a national banking association duly organized under the laws of the United States, as Trustee (herein called the “Trustee”) and ELAVON FINANCIAL SERVICES DAC,
as paying agent. 
 RECITALS 

WHEREAS, the Company and the Guarantors executed and delivered to the Trustee the Indenture, dated as of March 28, 2017 (the
“Base Indenture” and, together with this Supplemental Indenture, the “Indenture”), providing for the issuance from time to time of the Company’s Securities; 

WHEREAS, pursuant to the terms of the Base Indenture, the Company desires to provide for the establishment of six new series of its Securities
to be known as its 0.000% Senior Notes due 2023 (the “2023 Notes”), 0.000% Senior Notes due 2025 (the “2025 Notes”), 0.375% Senior Notes due 2028 (the “2028 Notes”), 0.750% Senior Notes due 2032
(the “2032 Notes”), 1.375% Senior Notes due 2040 (the “2040 Notes”) and 1.625% Senior Notes due 2050 (the “2050 Notes” and, together with the 2023 Notes, the 2025 Notes, the 2028 Notes, the
2032 Notes and the 2040 Notes, the “Notes”), to be fully and unconditionally guaranteed by the Guarantors (the “Guarantees”), the form and substance of such Notes and the terms, provisions and conditions thereof to
be set forth as provided in the Base Indenture and this Supplemental Indenture; 
 WHEREAS, the Company has requested that the Trustee and
the Paying Agent execute and deliver this Supplemental Indenture, and all requirements necessary to make this Supplemental Indenture a valid instrument in accordance with its terms, to make the Notes, when executed by the Company and authenticated
and delivered by the Trustee, the valid and legally binding obligations of the Company, to make the Guarantees, when executed by the Guarantors, the valid and legally binding obligations of the Guarantors, and all acts and things necessary have been
done and performed to make this Supplemental Indenture enforceable in accordance with its terms, and the execution and delivery of this Supplemental Indenture have been duly authorized in all respects. 

 WITNESSETH: 

NOW, THEREFORE, for and in consideration of the premises contained herein, each party agrees for the benefit of each other party and for the
equal and ratable benefit of the Holders of the Notes, as follows: 
 ARTICLE 1 

DEFINITIONS 

Section 1.01.    Capitalized terms used but not defined in this Supplemental Indenture shall have the meanings
ascribed to them in the Base Indenture. 
 Section 1.02.    References in this Supplemental Indenture to article
and section numbers shall be deemed to be references to article and section numbers of this Supplemental Indenture unless otherwise specified. 

Section 1.03.    For purposes of this Supplemental Indenture, the following terms have the meanings ascribed to them
as follows: 
 “2023 Notes” has the meaning provided in the recitals. 

“2025 Notes” has the meaning provided in the recitals. 

“2028 Notes” has the meaning provided in the recitals. 

“2032 Notes” has the meaning provided in the recitals. 

“2040 Notes” has the meaning provided in the recitals. 

“2050 Notes” has the meaning provided in the recitals. 

“Base Indenture” has the meaning provided in the recitals. 

“Business Day” means any day, other than a Saturday or Sunday, (1) which is not a day on which banking institutions in
The City of New York or London are authorized or required by law, regulation or executive order to close and (2) on which the Trans-European Automated Real-Time Gross Settlement Express Transfer system, or any successor thereto, is open. 

“Clearstream” means Clearstream Banking, société anonyme. 

“Company” has the meaning provided in the preamble. 

“Euro” and “€” means the single currency introduced at the third stage of the European Economic and
Monetary Union pursuant to the Treaty establishing the European Community, as amended. 
 “Euroclear” means Euroclear Bank
SA/NV, as operator of the Euroclear System. 

  
 3 

 “Guarantor” has the meaning provided in the preamble. 

“Indenture” has the meaning provided in the recitals. 

“Interest Payment Date” has the meaning provided in Section 2.04. 

“Medtronic, Inc.” has the meaning provided in the preamble. 

“Notes” has the meaning provided in the recitals. 

“Parent” has the meaning provided in the preamble. 

“Paying Agent” has the meaning provided in Section 2.03(d). 

“Supplemental Indenture” has the meaning provided in the preamble. 

“Trustee” has the meaning provided in the preamble. 

“U.S. Dollar” means the lawful currency of the United States of America. 

ARTICLE 2 
 GENERAL TERMS AND
CONDITIONS OF THE NOTES 
 Section 2.01.    Designation and Principal Amount. The 2023 Notes, the 2025
Notes, the 2028 Notes, the 2032 Notes, the 2040 Notes and the 2050 Notes are hereby authorized, each unlimited in aggregate principal amount. The 2023 Notes, the 2025 Notes, the 2028 Notes, the 2032 Notes, the 2040 Notes and the 2050 Notes issued on
the date hereof pursuant to the terms of this Indenture shall be in an aggregate principal amount of €1,250,000,000, €1,000,000,000, €1,000,000,000, €1,000,000,000, €1,000,000,000 and €1,000,000,000, respectively, which
amounts shall be set forth in the written order of the Company for the authentication and delivery of the Notes pursuant to Section 3.03 of the Base Indenture. In addition, the Company may, from time to time, without notice to or the consent of
the Holders of the Notes, create and issue additional Notes of any series ranking equally and ratably with the Notes of such series issued on the date hereof in all respects (or in all respects except for the payment of interest accruing prior to
the issue date of such additional Notes or except for the first payment of interest following the issue date of such additional Notes), so that such additional Notes shall be consolidated and form a single series with such series of Notes issued on
the date hereof and shall have the same terms as to status, redemption or otherwise as such series of Notes issued on the date hereof; provided, that if any such additional Notes are not fungible with the Notes of such series initially issued
hereunder for U.S. federal income tax purposes, such additional Notes shall have a separate CUSIP/ISIN number. 

Section 2.02.    Maturity. The principal amount of the 2023 Notes shall be payable on March 15, 2023, the
principal amount of the 2025 Notes shall be payable on October 15, 2025, the principal amount of the 2028 Notes shall be payable on October 15, 2028, the principal amount of the 2032 Notes shall be payable on October 15, 2032, the

  
 4 

 
principal amount of the 2040 Notes shall be payable on October 15, 2040 and the principal amount of the 2050 Notes shall be payable on October 15, 2050. 

Section 2.03.    Form and Payment. (a) The Notes shall be issued as global notes, only in fully
registered book-entry form, without coupons, in minimum denominations of €100,000 and integral multiples of €1,000 in excess thereof. 

(b)    Payments of principal, premium, if any, and/or interest, if any, on the global notes representing the Notes shall
be made to the Paying Agent (defined below) which in turn shall make payment to Euroclear and Clearstream as the Depositary with respect to the Notes of such series or its nominee. 

(c)    The global notes representing the Notes shall be deposited with, or on behalf of, the Depositary, and shall be
registered, at the request of the Depositary, in the name of the nominee of the Depositary, for Euroclear and Clearstream. 

(d)    The Company initially appoints U.S. Bank National Association as Security Registrar with respect to the Notes
pursuant to Section 3.05 of the Base Indenture until such time as the Security Registrar has resigned or a successor has been appointed. Elavon Financial Services DAC shall initially act as paying agent (the “Paying Agent”) for
the Notes. The Company may appoint and change the Paying Agent without prior notice to the Holders. 

Section 2.04.    Interest. Interest on the Notes shall accrue at the rate of 0.000% per annum for the 2023
Notes, 0.000% per annum for the 2025 Notes, 0.375% per annum for the 2028 Notes, 0.750% per annum for the 2032 Notes, 1.375% per annum for the 2040 Notes and 1.625% per annum for the 2050 Notes. Interest on the Notes shall be payable annually in
arrears, in respect of the 2023 Notes, on March 15, commencing on March 15, 2021 and in respect of the 2025 Notes, the 2028 Notes, the 2032 Notes, the 2040 Notes and the 2050 Notes, on October 15, commencing on October 15, 2021
(each such date, an “Interest Payment Date”), to the Holders in whose names the respective Notes are registered at the close of business on the Business Day (which shall for purposes of this Section 2.04 include only days on
which Clearstream and Euroclear are open for business) immediately preceding the applicable Interest Payment Date. Interest on the Notes shall be computed on the basis of the actual number of days in the period for which interest is being calculated
and the actual number of days from and including the last date on which interest was paid on the notes (or September 29, 2020, if no interest has been paid on the applicable series of Notes), to, but excluding, the next scheduled Interest
Payment Date. If any Interest Payment Date (other than a maturity date or redemption date) would otherwise be a day that is not a Business Day, such Interest Payment Date will be postponed to the next date that is a Business Day and no interest will
accrue on the amounts payable from and after such Interest Payment Date to the next Business Day. If the maturity date or redemption date of any series of Notes would fall on a day that is not a Business Day, then the related payment of principal,
premium, if any, and interest, if any, shall be made on the next succeeding Business Day with the same force and effect as if made on the date such payment was due, and no interest shall accrue on the amounts so payable for the period from and after
such date to the next Business Day. 

  
 5 

 Section 2.05.    Issuance in Euro. (a) Principal,
including any payments made upon any redemption or repurchase of the Notes, premium, if any, and interest payments, if any, in respect of the Notes will be payable in Euros. 

(b)    Distributions of principal, premium, if any, and interest, if any, with respect to any Global Security will be
credited in euros to the extent received by Euroclear or Clearstream from the Paying Agent to the cash accounts of Euroclear or Clearstream customers in accordance with the relevant system’s rules and procedures. 

(c)    If on or after the date hereof, the Euro is unavailable to the Company or, in the case of the Guarantees, Parent or
Medtronic, Inc., due to the imposition of exchange controls or other circumstances beyond the Company’s, Parent’s or Medtronic, Inc.’s control or if the Euro is no longer being used by the then member states of the European Economic
and Monetary Union that have adopted the Euro as their currency or for the settlement of transactions by public institutions of or within the international banking community, then all payments in respect of the Notes will be made in U.S. Dollars
until the Euro is again available to the Company or, in the case of the Guarantees, Parent or Medtronic, Inc., or so used. In such circumstances, the amount payable on any date in Euro will be converted by the Company into U.S. Dollars at the rate
mandated by the U.S. Federal Reserve Board as of the close of business on the second Business Day prior to the relevant Interest Payment Date or, in the event the U.S. Federal Reserve Board has not mandated a rate of conversion, on the basis of the
most recent U.S. Dollar/Euro exchange rate published in The Wall Street Journal on or prior to the second Business Day prior to the relevant payment date. Any payment in respect of the Notes so made in U.S. Dollars will not constitute an Event of
Default. Neither the Trustee nor the Paying Agent shall have any responsibility for any calculation or conversion in connection with this Section 2.05. 

Section 2.06.    Other Terms. The Notes shall be unsecured senior indebtedness of the Company and shall rank
equally and ratably in right of payment with all of the Company’s other unsecured and unsubordinated indebtedness outstanding from time to time. The Notes shall not be convertible into, or exchangeable for, any other securities of the Company,
except that the Notes shall be exchangeable for other Notes to the extent provided for in the Base Indenture. 
 ARTICLE 3 

REDEMPTION OF THE NOTES 

Section 3.01.    Optional Redemption. (a) The Company may redeem any series of the 2023 Notes, in whole
or in part, at any time prior to their maturity, and in the case of the 2025 Notes, the 2028 Notes, the 2032 Notes, the 2040 Notes and the 2050 Notes, at any time prior to the applicable Par Call Date, at a Redemption Price equal to the greater of:

 (i)    100% of the principal amount of the Notes to be redeemed, and 

  
 6 

 (ii)    the sum, as determined by a Quotation Agent, of
the present values of the Remaining Scheduled Payments of principal and interest on the Notes of such series to be redeemed (excluding any portion of such payments of interest accrued as of the Redemption Date and assuming that such Notes matured on
the applicable Par Call Date), discounted to the Redemption Date on an annual basis (ACTUAL/ACTUAL(ICMA)) at the Comparable Bond Rate, plus 15 basis points, in the case of the 2023 Notes, 15 basis points, in the case of the 2025 Notes, 20 basis
points, in the case of the 2028 Notes, 20 basis points, in the case of the 2032 Notes, 30 basis points, in the case of the 2040 Notes, and 30 basis points, in the case of the 2050 Notes; 

plus, in each case, accrued and unpaid interest, if any, to, but not including, the Redemption Date. 

(b)    At any time on and after the applicable Par Call Date, the Company may redeem the 2025 Notes, the 2028 Notes, the
2032 Notes, the 2040 Notes and the 2050 Notes at the Company’s option, in whole or in part, at a Redemption Price equal to 100% of the principal amount of the Notes to be redeemed, plus accrued and unpaid interest, if any, to, but not
including, the Redemption Date. 
 (c)    Notwithstanding anything to the contrary in the Base Indenture, in the case of
any redemption at the election of the Company, the Company shall, at least 10 days prior to the date on which the Company mails the notice of redemption to each holder (unless a shorter notice shall be satisfactory to the Trustee), notify the
Trustee and the Paying Agent of the applicable Redemption Date, of the principal amount of Notes of such series to be redeemed and, if applicable, of the tenor of the Notes to be redeemed. 

(d)    Notwithstanding anything to the contrary in the Base Indenture, (i) notice of redemption shall be delivered
not less than 10 nor more than 60 days prior to the applicable Redemption Date, to each Holder of Notes to be redeemed, at such Holder’s address appearing in the Security Register and (ii) an Officers’ Certificate specifying the
actual redemption price shall be sent to the Trustee no later than two Business Days prior to the Redemption Date. A notice of redemption may, at the discretion of the Company, be subject to one or more conditions precedent, including, but not
limited to, completion of an equity offering, a financing, or other corporate transaction, provided that if such redemption or notice is subject to satisfaction of one or more conditions precedent, such notice shall state that, in the Company’s
discretion, the redemption date may be postponed until up to 60 days following the notice of redemption, and such notice may be rescinded in the event that any or all such conditions shall not have been satisfied by the redemption date (including as
it may be postponed). 
 (e)    Notes may be redeemed in part in the minimum authorized denomination or in any integral
multiple of such amount. 

  
 7 

 (f)    For purposes of this Section 3.01, the following definitions
are applicable: 
 “Comparable Bond Rate” means, for any Redemption Date, the rate per annum equal to the annual equivalent
yield to maturity or interpolated yield to maturity (on a day count basis), computed as of the third Business Day immediately preceding that Redemption Date, of the Comparable Government Issue, assuming a price for the Comparable Government Issue
(expressed as a percentage of its principal amount) equal to the Comparable Price for such Redemption Date. 
 “Comparable
Government Issue” means the euro-denominated security issued by the German federal government selected by a Quotation Agent as having an actual or interpolated maturity comparable to the remaining term of the Notes to be redeemed (assuming,
in the case of the 2025 Notes, the 2028 Notes, the 2032 Notes, the 2040 Notes and the 2050 Notes, that such Notes matured on the applicable Par Call Date) that would be utilized, at the time of selection and in accordance with customary financial
practice, in pricing new issues of corporate debt securities of comparable maturity to the remaining term of the Notes to be redeemed. 

“Comparable Price” means, with respect to any Redemption Date, (i) the average of the Reference Dealer Quotations for
such Redemption Date, after excluding the highest and lowest of the Reference Dealer Quotations, (ii) if the Company obtains fewer than four Reference Dealer Quotations, the arithmetic average of all those Reference Dealer Quotations or
(iii) if the Company obtains only one Reference Dealer Quotation, such Reference Dealer Quotation. 
 “Par Call Date”
means in the case of the 2025 Notes, September 15, 2025; in the case of the 2028 Notes, July 15, 2028; in the case of the 2032 Notes, July 15, 2032; in the case of the 2040 Notes, April 15, 2040; and in the case of the 2050
Notes, April 15, 2050. 
 “Quotation Agent” means the Reference Dealer appointed by the Company. 

“Reference Dealer” means (i) each of Barclays Bank PLC, BofA Securities Europe SA, Mizuho Securities Europe GmbH and
Deutsche Bank Aktiengesellschaft and their respective successors; provided, however, that if any of the foregoing shall cease to be a broker or dealer of, and/or a market maker in, German government bonds (a “Primary Bond Dealer”),
the Company shall substitute another Primary Bond Dealer and (ii) any other Primary Bond Dealers selected by the Company. 

“Reference Dealer Quotations” means, with respect to each Reference Dealer and any Redemption Date, the average, as
determined by the Quotation Agent, of the bid and asked prices for the Comparable Government Issue (expressed in each case as a percentage of its principal amount) quoted in writing to the Quotation Agent by such Reference Dealer at 11:00 a.m.,
London time, on the third Business Day preceding such Redemption Date. 
 “Remaining Scheduled Payments” means, with
respect to each of the Notes to be redeemed, the remaining scheduled payments of the principal thereof and interest thereon that would be due after the related redemption date but for such redemption (assuming, in the case of the 2025 Notes, the
2028 Notes, the 2032 Notes, the 2040 Notes 

  
 8 

 
and the 2050 Notes, that the Notes to be redeemed matured on the applicable Par Call Date); provided, however, that if such Redemption Date is not an Interest Payment Date with respect to such
Note, the amount of the next succeeding scheduled interest payment thereon will be reduced by the amount of interest accrued thereon to such Redemption Date. 

Section 3.02.    Article 15 of the Base Indenture shall apply to each series of Notes; provided that the first
sentence of Section 15.01 shall be amended by inserting “Ireland” immediately after “Luxembourg,” therein. 

ARTICLE 4 
 MISCELLANEOUS 

Section 4.01.    Covenant Defeasance. Article 13 of the Base Indenture shall be applicable to the Notes. 

Section 4.02.    Form of Notes. (a) The Notes and the Trustee’s certificates of authentication to be
endorsed thereon are to be substantially in the forms of Exhibits A through F attached hereto, which forms are hereby incorporated in and made a part of this Supplemental Indenture. 

(b)    The terms and provisions contained in the Notes shall constitute, and are hereby expressly made, a part of this
Supplemental Indenture, and the Company, the Trustee and the Paying Agent, by their execution and delivery of this Supplemental Indenture, expressly agree to such terms and provisions and to be bound thereby. 

Section 4.03.    Ratification of Base Indenture. The Base Indenture, as supplemented by this Supplemental
Indenture, is in all respects ratified and confirmed, and this Supplemental Indenture shall be deemed part of the Base Indenture in the manner and to the extent herein and therein provided. 

Section 4.04.    Trust Indenture Act Controls. If any provision hereof limits, qualifies or conflicts with the
duties imposed by Section 310 through Section 317 of the Trust Indenture Act of 1939, the imposed duties shall control. 

Section 4.05.    Listing. Upon listing of the Notes of a series on the New York Stock Exchange, the Company
will use commercially reasonable efforts to maintain such listing and satisfy the requirements for such continued listing as long as the Notes of such series are outstanding. 

Section 4.06.    Conflict with Indenture. To the extent not expressly amended or modified by this Supplemental
Indenture, the Base Indenture shall remain in full force and effect. If any provision of this Supplemental Indenture relating to the Notes is inconsistent with any provision of the Base Indenture, the provision of this Supplemental Indenture shall
control. 

  
 9 

 Section 4.07.    Governing Law. THIS SUPPLEMENTAL INDENTURE
AND THE NOTES SHALL BE DEEMED TO BE A CONTRACT UNDER THE LAWS OF THE STATE OF NEW YORK, AND FOR ALL PURPOSES SHALL BE CONSTRUED IN ACCORDANCE WITH THE LAWS OF SUCH STATE, EXCEPT AS MAY OTHERWISE BE REQUIRED BY MANDATORY PROVISIONS OF LAW. FOR THE
AVOIDANCE OF DOUBT, THE APPLICABILITY OF ARTICLES 470-3 TO 470-19 OF THE LUXEMBOURG LAW ON COMMERCIAL COMPANIES DATED AUGUST 10, 1915 ON COMMERCIAL COMPANIES, AS
AMENDED, SHALL BE EXCLUDED. 
 Section 4.08.    Service of Process. The Company and each Guarantor appoints
Corporation Service Company, with offices at 80 State Street, Albany, New York 12207-2543, United States, as its agent to receive service of process or other legal summons for purposes of any suit, action or proceeding based on or arising out of or
relating to this Supplemental Indenture or any Notes or Guarantees. 
 Section 4.09.    Successors. All
agreements of the Company and the Guarantor in the Base Indenture, this Supplemental Indenture and the Notes shall bind their respective successors. All agreements of the Trustee in the Base Indenture and this Supplemental Indenture shall bind its
successors. 
 Section 4.10.     Counterparts. This instrument may be executed in any number of
counterparts, each of which so executed shall be deemed to be an original, but all such counterparts shall together constitute but one and the same instrument. Signatures of the parties hereto transmitted by facsimile or PDF shall be deemed to be
their original signatures for all purposes. 
 Section 4.11.    Trustee Disclaimer. The Trustee makes no
representation as to the validity or sufficiency of this Supplemental Indenture other than as to the validity of its execution and delivery by the Trustee. The recitals and statements herein are deemed to be those of the Company and the Guarantors
and not the Trustee. 

  
 10 

 IN WITNESS WHEREOF, the parties hereto have caused the Supplemental Indenture to be duly
executed as of the day and year first above written. 
  

			
	MEDTRONIC GLOBAL HOLDINGS S.C.A., a Luxembourg corporate partnership limited by shares (société en commandite par actions) represented by Medtronic Global Holdings GP S.à.r.l. its General
Partner, in turn acting by

 
			
		
	By:	 	 /s/ Erik De Gres

		 	Name: Erik De Gres
		 	Title: Managing Director and authorized signatory

 Attest: 
  

			
	By:	 	 /s/ Salvador Sens

		 	Name: Salvador Sens
		 	Title: Managing Director and authorized signatory of Medtronic Global Holdings S.C.A.

 [Signature Page to Medtronic Global Holdings S.C.A. Fourth Supplemental Indenture] 

 
			
	MEDTRONIC PUBLIC LIMITED COMPANY

 
			
		
	By:	 	 /s/ Jason Bristow

		 	Name: Jason Bristow
		 	Title: Treasurer

 [Signature Page to Medtronic Global Holdings S.C.A. Fourth Supplemental Indenture] 

 
			
	MEDTRONIC, INC.

 
			
		
	By:	 	 /s/ Jason Bristow

		 	 Name: Jason Bristow
 Title:
Treasurer

 [Signature Page to Medtronic Global Holdings S.C.A. Fourth Supplemental Indenture] 

 
			
	WELLS FARGO BANK, NATIONAL
ASSOCIATION, Trustee

 
			
		
	By:	 	 /s/ Stefan Victory

		 	Name: Stefan Victory
		 	Title: Vice President

 [Signature Page to Medtronic Global Holdings S.C.A. Fourth Supplemental Indenture] 

 
			
	 ELAVON FINANCIAL SERVICES DAC,
 as
Paying Agent

 
			
		
	By:	 	 /s/ Michael Leong

		 	Name: Michael Leong
		 	Title: Authorised Signatory

 [Signature Page to Medtronic Global Holdings S.C.A. Fourth Supplemental Indenture] 

 EXHIBIT A 

FORM OF NOTE 
 THIS
SECURITY IS A GLOBAL SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF A DEPOSITARY OR A NOMINEE THEREOF. THIS SECURITY MAY NOT BE EXCHANGED IN WHOLE OR IN PART FOR A SECURITY REGISTERED, AND NO
TRANSFER OF THIS SECURITY IN WHOLE OR IN PART MAY BE REGISTERED, IN THE NAME OF ANY PERSON OTHER THAN SUCH DEPOSITARY OR A NOMINEE THEREOF, EXCEPT IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE. 

UNLESS THIS CERTIFICATE IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF EUROCLEAR BANK SA/NV (“EUROCLEAR”) AND CLEARSTREAM BANKING,
S.A. (“CLEARSTREAM” AND, TOGETHER WITH EUROCLEAR, “EUROCLEAR/CLEARSTREAM”), TO THE COMPANY OR ITS AGENT FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF USB NOMINEES (UK)
LIMITED OR IN SUCH OTHER NAME AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF EUROCLEAR/CLEARSTREAM (AND ANY PAYMENT IS MADE TO USB NOMINEES (UK) LIMITED OR TO SUCH OTHER ENTITY AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF
EUROCLEAR/CLEARSTREAM), ANY TRANSFER, PLEDGE OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL INASMUCH AS THE REGISTERED OWNER HEREOF, ELAVON FINANCIAL SERVICES DAC, HAS AN INTEREST HEREIN. TRANSFERS OF THIS GLOBAL SECURITY
SHALL BE LIMITED TO TRANSFERS IN WHOLE, BUT NOT IN PART, TO NOMINEES OF USB NOMINEES (UK) LIMITED OR TO A SUCCESSOR THEREOF OR SUCH SUCCESSOR’S NOMINEE. 

 MEDTRONIC GLOBAL HOLDINGS S.C.A. 

0.000% Senior Note Due 2023 
  

			
		  	CUSIP No.: 58507L AR0
	 No.
	  	    ISIN No.: XS2240133459
		  	COMMON CODE: 224013345
		  	€            

 Medtronic Global Holdings S.C.A., a corporate partnership limited by shares (société en
commandite par actions) incorporated and existing under the laws of the Grand Duchy of Luxembourg (herein called the “Company”, which term includes any successor corporation under the Indenture hereinafter referred to), for
value received, hereby promises to pay to USB Nominees (UK) Limited or registered assigns, the principal sum of      Euros on March 15, 2023 and to pay interest thereon from September 29, 2020 or from the most recent
Interest Payment Date to which interest has been paid or duly provided for, annually in arrears on March 15 in each year, commencing March 15, 2021, at the rate of 0.000% per annum, until the principal hereof is paid or made available for
payment. The Company shall pay interest on overdue principal, and on overdue installments of interest (without regard to any applicable grace periods) to the extent lawful, from time to time on demand at the rate borne by this Security. 

The interest so payable, and punctually paid or duly provided for, on any Interest Payment Date will, as provided in such Indenture, be paid
to the Person in whose name this Security is registered at the close of business on the Regular Record Date for such interest, which shall be the Business Day immediately preceding such Interest Payment Date. Any such interest not so punctually paid
or duly provided for will forthwith cease to be payable to the Holder on such Regular Record Date and may either be paid to the Person in whose name this Security is registered at the close of business on a Special Record Date for the payment of
such Defaulted Interest to be fixed by the Trustee, notice whereof shall be given to Holders of Securities of this series not less than 10 days prior to such Special Record Date, or be paid at any time in any other lawful manner not inconsistent
with the requirements of any securities exchange on which the Securities of this series may be listed, and upon such notice as may be required by such exchange, all as more fully provided in said Indenture. 

Payment of the principal of (and premium, if any) and any such interest on this Security will be made at the office or agency of the Paying
Agent maintained for that purpose in London, Dublin or any financial center in a European Economic Area jurisdiction in Euro; provided, however, that at the option of the Company payment of interest may be made by check mailed to the address of the
Person entitled thereto as such address shall appear in the Security Register. If the Euro is unavailable to the Company due to the imposition of exchange controls or other circumstances beyond its control or the Euro is no longer used by the then
member states of the European Monetary Union that have adopted the Euro as their currency or for the settlement of transactions by public institutions of or within the international banking community, then all payments in respect of the 2023 Notes
will be made in U.S. Dollars until the Euro is again available to the Company or so used. In such circumstances, the amount payable on 

 
any date in Euro will be converted by the Company into U.S. Dollars at the rate mandated by the U.S. Federal Reserve Board as of the close of business on the second Business Day prior to the
relevant payment date or, in the event the U.S. Federal Reserve Board has not mandated a rate of conversion, on the basis of the most recent U.S. Dollar/Euro exchange rate published in The Wall Street Journal on or prior to the second Business Day
prior to the relevant payment date or, in the event The Wall Street Journal has not published such exchange rate, the rate will be determined in the Company’s sole discretion on the basis of the most recently available market exchange rate for
the Euro. For the avoidance of doubt, any such payment in respect of the 2023 Notes so made in U.S. Dollars will not constitute an Event of Default. Neither the Trustee nor the Paying Agent shall have any responsibility for any calculation or
conversion in connection with the foregoing. 
 Reference is hereby made to the further provisions of this Security set forth on the reverse
hereof, which further provisions shall for all purposes have the same effect as if set forth at this place. 
 Unless the certificate of
authentication hereon has been executed by the Trustee referred to on the reverse hereof by manual signature, this Security shall not be entitled to any benefit under the Indenture or be valid or obligatory for any purpose. 

 IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed under its
corporate seal. 
  

			
	MEDTRONIC GLOBAL HOLDINGS S.C.A., a Luxembourg corporate partnership limited by shares (société en commandite par actions) represented by Medtronic Global Holdings GP S.à.r.l. its General
Partner, in turn acting by

 
			
		
	By:	 	  

		 	Name:
		 	Title:

 Attest: 

 NOTATION OF GUARANTEE 

For value received, the undersigned (the “Guarantor”), to the extent set forth in and subject to the terms of the Indenture,
dated as of March 28, 2017 (the “Base Indenture”), among Medtronic Global Holdings S.C.A., a corporate partnership limited by shares (société en commandite par actions) incorporated and existing under the
laws of the Grand Duchy of Luxembourg (the “Company”), Medtronic Public Limited Company, a public limited company incorporated under the laws of Ireland (“Medtronic plc”), Medtronic, Inc., a Minnesota corporation
(“Medtronic, Inc.”), and Wells Fargo Bank, National Association, as Trustee (herein called the “Trustee”, which term includes any successor trustee under the Indenture (as defined below)), and as amended and
supplemented by the Fourth Supplemental Indenture, dated as of September 29, 2020 (the “Fourth Supplemental Indenture” and, together with the Base Indenture, the “Indenture”), among the Company, Medtronic plc,
Medtronic, Inc., the Trustee and Elavon Financial Services DAC, hereby fully and unconditionally guarantees, on a joint and several basis, to each Holder and to the Trustee and its successors and assigns, that the principal of and premium, if any,
and interest on the 2023 Notes shall be promptly paid in full when due, whether at Stated Maturity, by acceleration, redemption or otherwise, and interest on the overdue principal of and interest on the 2023 Notes, if any, if lawful, and all other
obligations of the Company to the Holders or the Trustee hereunder or thereunder shall be promptly paid in full or performed. 
 The
obligations of each Guarantor to the Holders and to the Trustee pursuant to this Notation of Guarantee and the Indenture are expressly set forth in Article 14 of the Indenture, and reference is hereby made to the Indenture for the precise terms and
limitations of this Notation of Guarantee. Each Holder of the 2023 Notes to which this Notation of Guarantee is endorsed, by accepting such 2023 Notes, agrees to and shall be bound by such provisions. 

All terms used in this Notation of Guarantee which are defined in the Indenture shall have the meanings assigned to them in the Indenture.

 IN WITNESS WHEREOF, each Guarantor has caused this Notation of Guarantee to be signed by a
duly authorized officer. 
 Dated:     , 20 

 

			
	MEDTRONIC PUBLIC LIMITED COMPANY

 
			
		
	By	 	  

 
			
	
	MEDTRONIC, INC.

 
			
		
	By	 	  

 This is one of the Securities of the series designated herein and referred to in the
within-mentioned Indenture. 
 Dated:      , 20 

 

			
	WELLS FARGO BANK, NATIONAL
ASSOCIATION, Trustee

 
			
		
	By:	 	  

		 	Authorized Signatory

 (REVERSE OF SECURITY) 

MEDTRONIC GLOBAL HOLDINGS S.C.A. 

0.000% Senior Note Due 2023 

This Security is one of a duly authorized issue of securities of the Company (herein called the “Securities”), issued and to
be issued in one or more series under an Indenture, dated as of March 28, 2017 (the “Base Indenture”), among the Company, Medtronic Public Limited Company, a public limited company incorporated under the laws of Ireland
(“Medtronic plc”), Medtronic, Inc., a Minnesota corporation (“Medtronic, Inc.”), and Wells Fargo Bank, National Association, as Trustee (herein called the “Trustee”, which term includes any
successor trustee under the Indenture (as defined below)), and as amended and supplemented by the Fourth Supplemental Indenture, dated as of September 29, 2020 (the “Fourth Supplemental Indenture” and, together with the Base
Indenture, the “Indenture”), among the Company, Medtronic plc, Medtronic, Inc., the Trustee and Elavon Financial Services DAC, and reference is hereby made to the Indenture for a statement of the respective rights, limitations of
rights, duties and immunities thereunder of the Company, the Trustee and the Holders of the Securities and of the terms upon which the Securities are, and are to be, authenticated and delivered. This Security is one of the series designated on the
face hereof, initially limited in aggregate principal amount to €1,250,000,000. The Company may at any time issue additional Securities under the Indenture in unlimited amounts having the same terms as the Securities; provided that no
additional Securities may be issued if an Event of Default has occurred and is continuing with respect to the Securities. 
 The Securities
of this series may be redeemed at any time prior to their maturity, as a whole or in part, at the option of the Company, upon mailing notice of such redemption not less than 10 and not more than 60 days prior to the applicable Redemption Date to the
Holders of such Securities, at a Redemption Price equal to the greater of: 
 (i) 100% of the principal amount of the
Securities being redeemed; and 
 (ii) the sum, as determined by a Quotation Agent, of the present values of the Remaining
Scheduled Payments of principal and interest on the Securities to be redeemed (excluding any portion of such payments of interest accrued as of the Redemption Date), discounted to the Redemption Date on an annual basis (ACTUAL/ACTUAL(ICMA)) at the
Comparable Bond Rate, plus 15 basis points; 
 plus, in each case, accrued and unpaid interest to, but not including, the Redemption Date. 

In the event of redemption of this Security in part only, a new Security or Securities of this series and of like tenor for the unredeemed
portion hereof will be issued in the name of the Holder hereof upon the cancellation hereof. 
 If an Event of Default with respect to
Securities of this series shall occur and be continuing, the principal of the Securities of this series may be declared due and payable in the manner and with the effect provided in the Indenture. 

 The Indenture permits, with certain exceptions as therein provided, the amendment thereof
and the modification of the rights and obligations of the Company and the rights of the Holders of the Securities of each series to be affected under the Indenture at any time by the Company and the Trustee with the consent of the Holders of a
majority in principal amount of the Securities at the time Outstanding of each series to be affected. The Indenture also contains provisions permitting the Holders of specified percentages in principal amount of the Securities of each series at the
time Outstanding, on behalf of the Holders of all Securities of such series, to waive compliance by the Company with certain provisions of the Indenture and certain past defaults under the Indenture and their consequences. Any such consent or waiver
by the Holder of this Security shall be conclusive and binding upon such Holder and upon all future Holders of this Security and of any Security issued upon the registration of transfer hereof or in exchange herefor or in lieu hereof, whether or not
notation of such consent or waiver is made upon this Security. 
 As provided in and subject to the provisions of the Indenture, the Holder
of this Security shall not have the right to institute any proceeding with respect to the Indenture or for the appointment of a receiver or trustee or for any other remedy thereunder, unless such Holder shall have previously given the Trustee
written notice of a continuing Event of Default with respect to the Securities of this series, the Holders of not less than 25% in principal amount of the Securities of this series at the time Outstanding shall have made written request to the
Trustee to institute proceedings in respect of such Event of Default as Trustee and offered the Trustee indemnity against the costs, expenses and liabilities to be incurred in compliance with such request, and the Trustee shall not have received
from the Holders of a majority in principal amount of Securities of this series at the time Outstanding a direction inconsistent with such request, and shall have failed to institute any such proceeding, for 60 days after receipt of such notice,
request and offer of indemnity. The foregoing shall not apply to any suit instituted by the Holder of this Security for the enforcement of any payment of principal hereof or any premium or interest hereon on or after the respective due dates
expressed herein. 
 As provided in the Indenture and subject to certain limitations therein set forth, the transfer of this Security is
registrable in the Security Register, upon surrender of this Security for registration of transfer at the office or agency of the Company in any place where the principal of and any premium and interest on this Security are payable, duly endorsed
by, or accompanied by a written instrument of transfer in form satisfactory to the Company and the Security Registrar duly executed by, the Holder hereof or the Holder’s attorney duly authorized in writing, and thereupon one or more new
Securities of this series and of like tenor, of authorized denominations and for the same aggregate principal amount, will be issued to the designated transferee or transferees. 

The Securities of this series are issuable only in registered form without coupons in denominations of €100,000 or an integral multiple
of €1,000 in excess thereof. As provided in the Indenture and subject to certain limitations therein set forth, Securities of this series are exchangeable for a like aggregate principal amount of Securities of this series and of like tenor of a
different authorized denomination, as requested by the Holder surrendering the same. 

 No service charge shall be made to a Holder for any such registration of transfer or
exchange, but the Company may require payment of a sum sufficient to cover any tax or other governmental charge payable in connection therewith. 

Prior to due presentment of this Security for registration of transfer, the Company, the Trustee and any agent of the Company or the Trustee
may treat the Person in whose name this Security is registered as the owner hereof for all purposes, whether or not this Security be overdue, and neither the Company, the Trustee nor any such agent shall be affected by notice to the contrary. 

Reference is made to the Indenture. Such further provisions shall for all purposes have the same effect as though fully set forth herein. 

All terms used in this Security which are defined in the Indenture shall have the meanings assigned to them in the Indenture. 

 EXHIBIT B 

FORM OF NOTE 
 THIS
SECURITY IS A GLOBAL SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF A DEPOSITARY OR A NOMINEE THEREOF. THIS SECURITY MAY NOT BE EXCHANGED IN WHOLE OR IN PART FOR A SECURITY REGISTERED, AND NO
TRANSFER OF THIS SECURITY IN WHOLE OR IN PART MAY BE REGISTERED, IN THE NAME OF ANY PERSON OTHER THAN SUCH DEPOSITARY OR A NOMINEE THEREOF, EXCEPT IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE. 

UNLESS THIS CERTIFICATE IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF EUROCLEAR BANK SA/NV (“EUROCLEAR”) AND CLEARSTREAM BANKING,
S.A. (“CLEARSTREAM” AND, TOGETHER WITH EUROCLEAR, “EUROCLEAR/CLEARSTREAM”), TO THE COMPANY OR ITS AGENT FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF USB NOMINEES (UK)
LIMITED OR IN SUCH OTHER NAME AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF EUROCLEAR/CLEARSTREAM (AND ANY PAYMENT IS MADE TO USB NOMINEES (UK) LIMITED OR TO SUCH OTHER ENTITY AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF
EUROCLEAR/CLEARSTREAM), ANY TRANSFER, PLEDGE OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL INASMUCH AS THE REGISTERED OWNER HEREOF, ELAVON FINANCIAL SERVICES DAC, HAS AN INTEREST HEREIN. TRANSFERS OF THIS GLOBAL SECURITY
SHALL BE LIMITED TO TRANSFERS IN WHOLE, BUT NOT IN PART, TO NOMINEES OF USB NOMINEES (UK) LIMITED OR TO A SUCCESSOR THEREOF OR SUCH SUCCESSOR’S NOMINEE. 

 MEDTRONIC GLOBAL HOLDINGS S.C.A. 

0.000% Senior Note Due 2025 
  

			
		  	CUSIP No.: 58507L AS8
	 No.     
	  	ISIN No.: XS2238787415
		  	COMMON CODE: 223878741
		  	€            

 Medtronic Global Holdings S.C.A., a corporate partnership limited by shares (société en
commandite par actions) incorporated and existing under the laws of the Grand Duchy of Luxembourg (herein called the “Company”, which term includes any successor corporation under the Indenture hereinafter referred to), for
value received, hereby promises to pay to USB Nominees (UK) Limited or registered assigns, the principal sum of      Euros on October 15, 2025 and to pay interest thereon from September 29, 2020 or from the most recent
Interest Payment Date to which interest has been paid or duly provided for, annually in arrears on October 15 in each year, commencing October 15, 2021, at the rate of 0.000% per annum, until the principal hereof is paid or made available
for payment. The Company shall pay interest on overdue principal, and on overdue installments of interest (without regard to any applicable grace periods) to the extent lawful, from time to time on demand at the rate borne by this Security. 

The interest so payable, and punctually paid or duly provided for, on any Interest Payment Date will, as provided in such Indenture, be paid
to the Person in whose name this Security is registered at the close of business on the Regular Record Date for such interest, which shall be the Business Day immediately preceding such Interest Payment Date. Any such interest not so punctually paid
or duly provided for will forthwith cease to be payable to the Holder on such Regular Record Date and may either be paid to the Person in whose name this Security is registered at the close of business on a Special Record Date for the payment of
such Defaulted Interest to be fixed by the Trustee, notice whereof shall be given to Holders of Securities of this series not less than 10 days prior to such Special Record Date, or be paid at any time in any other lawful manner not inconsistent
with the requirements of any securities exchange on which the Securities of this series may be listed, and upon such notice as may be required by such exchange, all as more fully provided in said Indenture. 

Payment of the principal of (and premium, if any) and any such interest on this Security will be made at the office or agency of the Paying
Agent maintained for that purpose in London, Dublin or any financial center in a European Economic Area jurisdiction in Euro; provided, however, that at the option of the Company payment of interest may be made by check mailed to the address of the
Person entitled thereto as such address shall appear in the Security Register. If the Euro is unavailable to the Company due to the imposition of exchange controls or other circumstances beyond its control or the Euro is no longer used by the then
member states of the European Monetary Union that have adopted the Euro as their currency or for the settlement of transactions by public institutions of or within the international banking community, then all payments in respect of the 2025 Notes
will be made in U.S. Dollars until the Euro is again available to the Company or so used. In such circumstances, the amount payable on 

 
any date in Euro will be converted by the Company into U.S. Dollars at the rate mandated by the U.S. Federal Reserve Board as of the close of business on the second Business Day prior to the
relevant payment date or, in the event the U.S. Federal Reserve Board has not mandated a rate of conversion, on the basis of the most recent U.S. Dollar/Euro exchange rate published in The Wall Street Journal on or prior to the second Business Day
prior to the relevant payment date or, in the event The Wall Street Journal has not published such exchange rate, the rate will be determined in the Company’s sole discretion on the basis of the most recently available market exchange rate for
the Euro. For the avoidance of doubt, any such payment in respect of the 2025 Notes so made in U.S. Dollars will not constitute an Event of Default. Neither the Trustee nor the Paying Agent shall have any responsibility for any calculation or
conversion in connection with the foregoing. 
 Reference is hereby made to the further provisions of this Security set forth on the reverse
hereof, which further provisions shall for all purposes have the same effect as if set forth at this place. 
 Unless the certificate of
authentication hereon has been executed by the Trustee referred to on the reverse hereof by manual signature, this Security shall not be entitled to any benefit under the Indenture or be valid or obligatory for any purpose. 

 IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed under its
corporate seal. 
  

			
	MEDTRONIC GLOBAL HOLDINGS S.C.A., a Luxembourg corporate partnership limited by shares (société en commandite par actions) represented by Medtronic Global Holdings GP S.à.r.l. its General
Partner, in turn acting by

 
			
		
	By:	 	  

		 	Name:
		 	Title:

 Attest: 

 NOTATION OF GUARANTEE 

For value received, the undersigned (the “Guarantor”), to the extent set forth in and subject to the terms of the Indenture,
dated as of March 28, 2017 (the “Base Indenture”), among Medtronic Global Holdings S.C.A., a corporate partnership limited by shares (société en commandite par actions) incorporated and existing under the
laws of the Grand Duchy of Luxembourg (the “Company”), Medtronic Public Limited Company, a public limited company incorporated under the laws of Ireland (“Medtronic plc”), Medtronic, Inc., a Minnesota corporation
(“Medtronic, Inc.”), and Wells Fargo Bank, National Association, as Trustee (herein called the “Trustee”, which term includes any successor trustee under the Indenture (as defined below)), and as amended and
supplemented by the Fourth Supplemental Indenture, dated as of September 29, 2020 (the “Fourth Supplemental Indenture” and, together with the Base Indenture, the “Indenture”), among the Company, Medtronic plc,
Medtronic, Inc., the Trustee and Elavon Financial Services DAC, hereby fully and unconditionally guarantees, on a joint and several basis, to each Holder and to the Trustee and its successors and assigns, that the principal of and premium, if any,
and interest on the 2025 Notes shall be promptly paid in full when due, whether at Stated Maturity, by acceleration, redemption or otherwise, and interest on the overdue principal of and interest on the 2025 Notes, if any, if lawful, and all other
obligations of the Company to the Holders or the Trustee hereunder or thereunder shall be promptly paid in full or performed. 
 The
obligations of each Guarantor to the Holders and to the Trustee pursuant to this Notation of Guarantee and the Indenture are expressly set forth in Article 14 of the Indenture, and reference is hereby made to the Indenture for the precise terms and
limitations of this Notation of Guarantee. Each Holder of the 2025 Notes to which this Notation of Guarantee is endorsed, by accepting such 2025 Notes, agrees to and shall be bound by such provisions. 

All terms used in this Notation of Guarantee which are defined in the Indenture shall have the meanings assigned to them in the Indenture.

 IN WITNESS WHEREOF, each Guarantor has caused this Notation of Guarantee to be signed by a
duly authorized officer. 
 Dated:     , 20 

 

			
	MEDTRONIC PUBLIC LIMITED COMPANY

 
			
		
	By	 	  

 
			
	
	MEDTRONIC, INC.

 
			
		
	By	 	  

 This is one of the Securities of the series designated herein and referred to in the
within-mentioned Indenture. 
 Dated:      , 20 

 

			
	WELLS FARGO BANK, NATIONAL
ASSOCIATION, Trustee
		
	By:	 	  

		 	Authorized Signatory

 (REVERSE OF SECURITY) 

MEDTRONIC GLOBAL HOLDINGS S.C.A. 

0.000% Senior Note Due 2025 

This Security is one of a duly authorized issue of securities of the Company (herein called the “Securities”), issued and to
be issued in one or more series under an Indenture, dated as of March 28, 2017 (the “Base Indenture”), among the Company, Medtronic Public Limited Company, a public limited company incorporated under the laws of Ireland
(“Medtronic plc”), Medtronic, Inc., a Minnesota corporation (“Medtronic, Inc.”), and Wells Fargo Bank, National Association, as Trustee (herein called the “Trustee”, which term includes any
successor trustee under the Indenture (as defined below)), and as amended and supplemented by the Fourth Supplemental Indenture, dated as of September 29, 2020 (the “Fourth Supplemental Indenture” and, together with the Base
Indenture, the “Indenture”), among the Company, Medtronic plc, Medtronic, Inc., the Trustee and Elavon Financial Services DAC, and reference is hereby made to the Indenture for a statement of the respective rights, limitations of
rights, duties and immunities thereunder of the Company, the Trustee and the Holders of the Securities and of the terms upon which the Securities are, and are to be, authenticated and delivered. This Security is one of the series designated on the
face hereof, initially limited in aggregate principal amount to €1,000,000,000. The Company may at any time issue additional Securities under the Indenture in unlimited amounts having the same terms as the Securities; provided that no
additional Securities may be issued if an Event of Default has occurred and is continuing with respect to the Securities. 
 The Securities
of this series may be redeemed at any time prior to the applicable Par Call Date, as a whole or in part, at the option of the Company, upon mailing notice of such redemption not less than 10 and not more than 60 days prior to the applicable
Redemption Date to the Holders of such Securities, at a Redemption Price equal to the greater of: 
 (i) 100% of the
principal amount of the Securities being redeemed; and 
 (ii) the sum, as determined by a Quotation Agent, of the present
values of the Remaining Scheduled Payments of principal and interest on the Securities to be redeemed (excluding any portion of such payments of interest accrued as of the Redemption Date and assuming that such Securities matured on the applicable
Par Call Date), discounted to the Redemption Date on an annual basis (ACTUAL/ACTUAL(ICMA)) at the Comparable Bond Rate, plus 15 basis points; 
 plus, in
each case, accrued and unpaid interest to, but not including, the Redemption Date. 
 In addition, at any time on and after the applicable
Par Call Date, the Securities are redeemable at the Company’s option, in whole or in part, at a Redemption Price equal to 100% of the principal amount of the Securities to be redeemed, plus accrued and unpaid interest, if any, to, but not
including, the Redemption Date. 

 In the event of redemption of this Security in part only, a new Security or Securities of
this series and of like tenor for the unredeemed portion hereof will be issued in the name of the Holder hereof upon the cancellation hereof. 

If an Event of Default with respect to Securities of this series shall occur and be continuing, the principal of the Securities of this series
may be declared due and payable in the manner and with the effect provided in the Indenture. 
 The Indenture permits, with certain
exceptions as therein provided, the amendment thereof and the modification of the rights and obligations of the Company and the rights of the Holders of the Securities of each series to be affected under the Indenture at any time by the Company and
the Trustee with the consent of the Holders of a majority in principal amount of the Securities at the time Outstanding of each series to be affected. The Indenture also contains provisions permitting the Holders of specified percentages in
principal amount of the Securities of each series at the time Outstanding, on behalf of the Holders of all Securities of such series, to waive compliance by the Company with certain provisions of the Indenture and certain past defaults under the
Indenture and their consequences. Any such consent or waiver by the Holder of this Security shall be conclusive and binding upon such Holder and upon all future Holders of this Security and of any Security issued upon the registration of transfer
hereof or in exchange herefor or in lieu hereof, whether or not notation of such consent or waiver is made upon this Security. 
 As
provided in and subject to the provisions of the Indenture, the Holder of this Security shall not have the right to institute any proceeding with respect to the Indenture or for the appointment of a receiver or trustee or for any other remedy
thereunder, unless such Holder shall have previously given the Trustee written notice of a continuing Event of Default with respect to the Securities of this series, the Holders of not less than 25% in principal amount of the Securities of this
series at the time Outstanding shall have made written request to the Trustee to institute proceedings in respect of such Event of Default as Trustee and offered the Trustee indemnity against the costs, expenses and liabilities to be incurred in
compliance with such request, and the Trustee shall not have received from the Holders of a majority in principal amount of Securities of this series at the time Outstanding a direction inconsistent with such request, and shall have failed to
institute any such proceeding, for 60 days after receipt of such notice, request and offer of indemnity. The foregoing shall not apply to any suit instituted by the Holder of this Security for the enforcement of any payment of principal hereof or
any premium or interest hereon on or after the respective due dates expressed herein. 
 As provided in the Indenture and subject to certain
limitations therein set forth, the transfer of this Security is registrable in the Security Register, upon surrender of this Security for registration of transfer at the office or agency of the Company in any place where the principal of and any
premium and interest on this Security are payable, duly endorsed by, or accompanied by a written instrument of transfer in form satisfactory to the Company and the Security Registrar duly executed by, the Holder hereof or the Holder’s attorney
duly authorized in writing, and thereupon one or more new Securities of this series and of like tenor, of authorized denominations and for the same aggregate principal amount, will be issued to the designated transferee or transferees. 

 The Securities of this series are issuable only in registered form without coupons in
denominations of €100,000 or an integral multiple of €1,000 in excess thereof. As provided in the Indenture and subject to certain limitations therein set forth, Securities of this series are exchangeable for a like aggregate principal
amount of Securities of this series and of like tenor of a different authorized denomination, as requested by the Holder surrendering the same. 

No service charge shall be made to a Holder for any such registration of transfer or exchange, but the Company may require payment of a sum
sufficient to cover any tax or other governmental charge payable in connection therewith. 
 Prior to due presentment of this Security for
registration of transfer, the Company, the Trustee and any agent of the Company or the Trustee may treat the Person in whose name this Security is registered as the owner hereof for all purposes, whether or not this Security be overdue, and neither
the Company, the Trustee nor any such agent shall be affected by notice to the contrary. 
 Reference is made to the Indenture. Such further
provisions shall for all purposes have the same effect as though fully set forth herein. 
 All terms used in this Security which are
defined in the Indenture shall have the meanings assigned to them in the Indenture. 

 EXHIBIT C 

FORM OF NOTE 
 THIS
SECURITY IS A GLOBAL SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF A DEPOSITARY OR A NOMINEE THEREOF. THIS SECURITY MAY NOT BE EXCHANGED IN WHOLE OR IN PART FOR A SECURITY REGISTERED, AND NO
TRANSFER OF THIS SECURITY IN WHOLE OR IN PART MAY BE REGISTERED, IN THE NAME OF ANY PERSON OTHER THAN SUCH DEPOSITARY OR A NOMINEE THEREOF, EXCEPT IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE. 

UNLESS THIS CERTIFICATE IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF EUROCLEAR BANK SA/NV (“EUROCLEAR”) AND CLEARSTREAM BANKING,
S.A. (“CLEARSTREAM” AND, TOGETHER WITH EUROCLEAR, “EUROCLEAR/CLEARSTREAM”), TO THE COMPANY OR ITS AGENT FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF USB NOMINEES (UK)
LIMITED OR IN SUCH OTHER NAME AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF EUROCLEAR/CLEARSTREAM (AND ANY PAYMENT IS MADE TO USB NOMINEES (UK) LIMITED OR TO SUCH OTHER ENTITY AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF
EUROCLEAR/CLEARSTREAM), ANY TRANSFER, PLEDGE OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL INASMUCH AS THE REGISTERED OWNER HEREOF, ELAVON FINANCIAL SERVICES DAC, HAS AN INTEREST HEREIN. TRANSFERS OF THIS GLOBAL SECURITY
SHALL BE LIMITED TO TRANSFERS IN WHOLE, BUT NOT IN PART, TO NOMINEES OF USB NOMINEES (UK) LIMITED OR TO A SUCCESSOR THEREOF OR SUCH SUCCESSOR’S NOMINEE. 

 MEDTRONIC GLOBAL HOLDINGS S.C.A. 

0.375% Senior Note Due 2028 
  

			
		  	CUSIP No.: 58507L AT6
	 No.
	  	    ISIN No.: XS2238789460
		  	COMMON CODE: 223878946
		  	€            

 Medtronic Global Holdings S.C.A., a corporate partnership limited by shares (société en
commandite par actions) incorporated and existing under the laws of the Grand Duchy of Luxembourg (herein called the “Company”, which term includes any successor corporation under the Indenture hereinafter referred to), for
value received, hereby promises to pay to USB Nominees (UK) Limited or registered assigns, the principal sum of      Euros on October 15, 2028 and to pay interest thereon from September 29, 2020 or from the most recent
Interest Payment Date to which interest has been paid or duly provided for, annually in arrears on October 15 in each year, commencing October 15, 2021, at the rate of 0.375% per annum, until the principal hereof is paid or made available
for payment. The Company shall pay interest on overdue principal, and on overdue installments of interest (without regard to any applicable grace periods) to the extent lawful, from time to time on demand at the rate borne by this Security. 

The interest so payable, and punctually paid or duly provided for, on any Interest Payment Date will, as provided in such Indenture, be paid
to the Person in whose name this Security is registered at the close of business on the Regular Record Date for such interest, which shall be the Business Day immediately preceding such Interest Payment Date. Any such interest not so punctually paid
or duly provided for will forthwith cease to be payable to the Holder on such Regular Record Date and may either be paid to the Person in whose name this Security is registered at the close of business on a Special Record Date for the payment of
such Defaulted Interest to be fixed by the Trustee, notice whereof shall be given to Holders of Securities of this series not less than 10 days prior to such Special Record Date, or be paid at any time in any other lawful manner not inconsistent
with the requirements of any securities exchange on which the Securities of this series may be listed, and upon such notice as may be required by such exchange, all as more fully provided in said Indenture. 

Payment of the principal of (and premium, if any) and any such interest on this Security will be made at the office or agency of the Paying
Agent maintained for that purpose in London, Dublin or any financial center in a European Economic Area jurisdiction in Euro; provided, however, that at the option of the Company payment of interest may be made by check mailed to the address of the
Person entitled thereto as such address shall appear in the Security Register. If the Euro is unavailable to the Company due to the imposition of exchange controls or other circumstances beyond its control or the Euro is no longer used by the then
member states of the European Monetary Union that have adopted the Euro as their currency or for the settlement of transactions by public institutions of or within the international banking community, then all payments in respect of the 2028 Notes
will be made in U.S. Dollars until the Euro is again available to the Company or so used. In such circumstances, the amount payable on 

 
any date in Euro will be converted by the Company into U.S. Dollars at the rate mandated by the U.S. Federal Reserve Board as of the close of business on the second Business Day prior to the
relevant payment date or, in the event the U.S. Federal Reserve Board has not mandated a rate of conversion, on the basis of the most recent U.S. Dollar/Euro exchange rate published in The Wall Street Journal on or prior to the second Business Day
prior to the relevant payment date or, in the event The Wall Street Journal has not published such exchange rate, the rate will be determined in the Company’s sole discretion on the basis of the most recently available market exchange rate for
the Euro. For the avoidance of doubt, any such payment in respect of the 2028 Notes so made in U.S. Dollars will not constitute an Event of Default. Neither the Trustee nor the Paying Agent shall have any responsibility for any calculation or
conversion in connection with the foregoing. 
 Reference is hereby made to the further provisions of this Security set forth on the reverse
hereof, which further provisions shall for all purposes have the same effect as if set forth at this place. 
 Unless the certificate of
authentication hereon has been executed by the Trustee referred to on the reverse hereof by manual signature, this Security shall not be entitled to any benefit under the Indenture or be valid or obligatory for any purpose. 

 IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed under its
corporate seal. 
  

			
	MEDTRONIC GLOBAL HOLDINGS S.C.A., a Luxembourg corporate partnership limited by shares (société en commandite par actions) represented by Medtronic Global Holdings GP S.à.r.l. its General
Partner, in turn acting by

 
			
		
	By:	 	  

		 	Name:
		 	Title:

 Attest: 

 NOTATION OF GUARANTEE 

For value received, the undersigned (the “Guarantor”), to the extent set forth in and subject to the terms of the Indenture,
dated as of March 28, 2017 (the “Base Indenture”), among Medtronic Global Holdings S.C.A., a corporate partnership limited by shares (société en commandite par actions) incorporated and existing under the
laws of the Grand Duchy of Luxembourg (the “Company”), Medtronic Public Limited Company, a public limited company incorporated under the laws of Ireland (“Medtronic plc”), Medtronic, Inc., a Minnesota corporation
(“Medtronic, Inc.”), and Wells Fargo Bank, National Association, as Trustee (herein called the “Trustee”, which term includes any successor trustee under the Indenture (as defined below)), and as amended and
supplemented by the Fourth Supplemental Indenture, dated as of September 29, 2020 (the “Fourth Supplemental Indenture” and, together with the Base Indenture, the “Indenture”), among the Company, Medtronic plc,
Medtronic, Inc., the Trustee and Elavon Financial Services DAC, hereby fully and unconditionally guarantees, on a joint and several basis, to each Holder and to the Trustee and its successors and assigns, that the principal of and premium, if any,
and interest on the 2028 Notes shall be promptly paid in full when due, whether at Stated Maturity, by acceleration, redemption or otherwise, and interest on the overdue principal of and interest on the 2028 Notes, if any, if lawful, and all other
obligations of the Company to the Holders or the Trustee hereunder or thereunder shall be promptly paid in full or performed. 
 The
obligations of each Guarantor to the Holders and to the Trustee pursuant to this Notation of Guarantee and the Indenture are expressly set forth in Article 14 of the Indenture, and reference is hereby made to the Indenture for the precise terms and
limitations of this Notation of Guarantee. Each Holder of the 2028 Notes to which this Notation of Guarantee is endorsed, by accepting such 2028 Notes, agrees to and shall be bound by such provisions. 

All terms used in this Notation of Guarantee which are defined in the Indenture shall have the meanings assigned to them in the Indenture.

 IN WITNESS WHEREOF, each Guarantor has caused this Notation of Guarantee to be signed by a
duly authorized officer. 
 Dated:     , 20 

 

			
	MEDTRONIC PUBLIC LIMITED COMPANY

 
			
		
	By	 	  

 
			
	
	MEDTRONIC, INC.

 
			
		
	By	 	  

 This is one of the Securities of the series designated herein and referred to in the
within-mentioned Indenture. 
 Dated:      , 20 

 

			
	WELLS FARGO BANK, NATIONAL ASSOCIATION, Trustee

 
			
		
	By:	 	  

		 	Authorized Signatory

 (REVERSE OF SECURITY) 

MEDTRONIC GLOBAL HOLDINGS S.C.A. 

0.375% Senior Note Due 2028 

This Security is one of a duly authorized issue of securities of the Company (herein called the “Securities”), issued and to
be issued in one or more series under an Indenture, dated as of March 28, 2017 (the “Base Indenture”), among the Company, Medtronic Public Limited Company, a public limited company incorporated under the laws of Ireland
(“Medtronic plc”), Medtronic, Inc., a Minnesota corporation (“Medtronic, Inc.”), and Wells Fargo Bank, National Association, as Trustee (herein called the “Trustee”, which term includes any
successor trustee under the Indenture (as defined below)), and as amended and supplemented by the Fourth Supplemental Indenture, dated as of September 29, 2020 (the “Fourth Supplemental Indenture” and, together with the Base
Indenture, the “Indenture”), among the Company, Medtronic plc, Medtronic, Inc., the Trustee and Elavon Financial Services DAC, and reference is hereby made to the Indenture for a statement of the respective rights, limitations of
rights, duties and immunities thereunder of the Company, the Trustee and the Holders of the Securities and of the terms upon which the Securities are, and are to be, authenticated and delivered. This Security is one of the series designated on the
face hereof, initially limited in aggregate principal amount to €1,000,000,000. The Company may at any time issue additional Securities under the Indenture in unlimited amounts having the same terms as the Securities; provided that no
additional Securities may be issued if an Event of Default has occurred and is continuing with respect to the Securities. 
 The Securities
of this series may be redeemed at any time prior to the applicable Par Call Date, as a whole or in part, at the option of the Company, upon mailing notice of such redemption not less than 10 and not more than 60 days prior to the applicable
Redemption Date to the Holders of such Securities, at a Redemption Price equal to the greater of: 
 (i) 100% of the
principal amount of the Securities being redeemed; and 
 (ii) the sum, as determined by a Quotation Agent, of the present
values of the Remaining Scheduled Payments of principal and interest on the Securities to be redeemed (excluding any portion of such payments of interest accrued as of the Redemption Date and assuming that such Securities matured on the applicable
Par Call Date), discounted to the Redemption Date on an annual basis (ACTUAL/ACTUAL(ICMA)) at the Comparable Bond Rate, plus 20 basis points; 
 plus, in
each case, accrued and unpaid interest to, but not including, the Redemption Date. 
 In addition, at any time on and after the applicable
Par Call Date, the Securities are redeemable at the Company’s option, in whole or in part, at a Redemption Price equal to 100% of the principal amount of the Securities to be redeemed, plus accrued and unpaid interest, if any, to, but not
including, the Redemption Date. 

 In the event of redemption of this Security in part only, a new Security or Securities of
this series and of like tenor for the unredeemed portion hereof will be issued in the name of the Holder hereof upon the cancellation hereof. 

If an Event of Default with respect to Securities of this series shall occur and be continuing, the principal of the Securities of this series
may be declared due and payable in the manner and with the effect provided in the Indenture. 
 The Indenture permits, with certain
exceptions as therein provided, the amendment thereof and the modification of the rights and obligations of the Company and the rights of the Holders of the Securities of each series to be affected under the Indenture at any time by the Company and
the Trustee with the consent of the Holders of a majority in principal amount of the Securities at the time Outstanding of each series to be affected. The Indenture also contains provisions permitting the Holders of specified percentages in
principal amount of the Securities of each series at the time Outstanding, on behalf of the Holders of all Securities of such series, to waive compliance by the Company with certain provisions of the Indenture and certain past defaults under the
Indenture and their consequences. Any such consent or waiver by the Holder of this Security shall be conclusive and binding upon such Holder and upon all future Holders of this Security and of any Security issued upon the registration of transfer
hereof or in exchange herefor or in lieu hereof, whether or not notation of such consent or waiver is made upon this Security. 
 As
provided in and subject to the provisions of the Indenture, the Holder of this Security shall not have the right to institute any proceeding with respect to the Indenture or for the appointment of a receiver or trustee or for any other remedy
thereunder, unless such Holder shall have previously given the Trustee written notice of a continuing Event of Default with respect to the Securities of this series, the Holders of not less than 25% in principal amount of the Securities of this
series at the time Outstanding shall have made written request to the Trustee to institute proceedings in respect of such Event of Default as Trustee and offered the Trustee indemnity against the costs, expenses and liabilities to be incurred in
compliance with such request, and the Trustee shall not have received from the Holders of a majority in principal amount of Securities of this series at the time Outstanding a direction inconsistent with such request, and shall have failed to
institute any such proceeding, for 60 days after receipt of such notice, request and offer of indemnity. The foregoing shall not apply to any suit instituted by the Holder of this Security for the enforcement of any payment of principal hereof or
any premium or interest hereon on or after the respective due dates expressed herein. 
 As provided in the Indenture and subject to certain
limitations therein set forth, the transfer of this Security is registrable in the Security Register, upon surrender of this Security for registration of transfer at the office or agency of the Company in any place where the principal of and any
premium and interest on this Security are payable, duly endorsed by, or accompanied by a written instrument of transfer in form satisfactory to the Company and the Security Registrar duly executed by, the Holder hereof or the Holder’s attorney
duly authorized in writing, and thereupon one or more new Securities of this series and of like tenor, of authorized denominations and for the same aggregate principal amount, will be issued to the designated transferee or transferees. 

 The Securities of this series are issuable only in registered form without coupons in
denominations of €100,000 or an integral multiple of €1,000 in excess thereof. As provided in the Indenture and subject to certain limitations therein set forth, Securities of this series are exchangeable for a like aggregate principal
amount of Securities of this series and of like tenor of a different authorized denomination, as requested by the Holder surrendering the same. 

No service charge shall be made to a Holder for any such registration of transfer or exchange, but the Company may require payment of a sum
sufficient to cover any tax or other governmental charge payable in connection therewith. 
 Prior to due presentment of this Security for
registration of transfer, the Company, the Trustee and any agent of the Company or the Trustee may treat the Person in whose name this Security is registered as the owner hereof for all purposes, whether or not this Security be overdue, and neither
the Company, the Trustee nor any such agent shall be affected by notice to the contrary. 
 Reference is made to the Indenture. Such further
provisions shall for all purposes have the same effect as though fully set forth herein. 
 All terms used in this Security which are
defined in the Indenture shall have the meanings assigned to them in the Indenture. 

 EXHIBIT D 

FORM OF NOTE 
 THIS
SECURITY IS A GLOBAL SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF A DEPOSITARY OR A NOMINEE THEREOF. THIS SECURITY MAY NOT BE EXCHANGED IN WHOLE OR IN PART FOR A SECURITY REGISTERED, AND NO
TRANSFER OF THIS SECURITY IN WHOLE OR IN PART MAY BE REGISTERED, IN THE NAME OF ANY PERSON OTHER THAN SUCH DEPOSITARY OR A NOMINEE THEREOF, EXCEPT IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE. 

UNLESS THIS CERTIFICATE IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF EUROCLEAR BANK SA/NV (“EUROCLEAR”) AND CLEARSTREAM BANKING,
S.A. (“CLEARSTREAM” AND, TOGETHER WITH EUROCLEAR, “EUROCLEAR/CLEARSTREAM”), TO THE COMPANY OR ITS AGENT FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF USB NOMINEES (UK)
LIMITED OR IN SUCH OTHER NAME AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF EUROCLEAR/CLEARSTREAM (AND ANY PAYMENT IS MADE TO USB NOMINEES (UK) LIMITED OR TO SUCH OTHER ENTITY AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF
EUROCLEAR/CLEARSTREAM), ANY TRANSFER, PLEDGE OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL INASMUCH AS THE REGISTERED OWNER HEREOF, ELAVON FINANCIAL SERVICES DAC, HAS AN INTEREST HEREIN. TRANSFERS OF THIS GLOBAL SECURITY
SHALL BE LIMITED TO TRANSFERS IN WHOLE, BUT NOT IN PART, TO NOMINEES OF USB NOMINEES (UK) LIMITED OR TO A SUCCESSOR THEREOF OR SUCH SUCCESSOR’S NOMINEE. 

 MEDTRONIC GLOBAL HOLDINGS S.C.A. 

0.750% Senior Note Due 2032 
  

			
		 	CUSIP No.: 58507L AU3
	 No.
	 	    ISIN No.: XS2238792175
		 	COMMON CODE: 223879217
		 	€            

 Medtronic Global Holdings S.C.A., a corporate partnership limited by shares (société en
commandite par actions) incorporated and existing under the laws of the Grand Duchy of Luxembourg (herein called the “Company”, which term includes any successor corporation under the Indenture hereinafter referred to), for
value received, hereby promises to pay to USB Nominees (UK) Limited or registered assigns, the principal sum of      Euros on October 15, 2032 and to pay interest thereon from September 29, 2020 or from the most recent
Interest Payment Date to which interest has been paid or duly provided for, annually in arrears on October 15 in each year, commencing October 15, 2021, at the rate of 0.750% per annum, until the principal hereof is paid or made available
for payment. The Company shall pay interest on overdue principal, and on overdue installments of interest (without regard to any applicable grace periods) to the extent lawful, from time to time on demand at the rate borne by this Security. 

The interest so payable, and punctually paid or duly provided for, on any Interest Payment Date will, as provided in such Indenture, be paid
to the Person in whose name this Security is registered at the close of business on the Regular Record Date for such interest, which shall be the Business Day immediately preceding such Interest Payment Date. Any such interest not so punctually paid
or duly provided for will forthwith cease to be payable to the Holder on such Regular Record Date and may either be paid to the Person in whose name this Security is registered at the close of business on a Special Record Date for the payment of
such Defaulted Interest to be fixed by the Trustee, notice whereof shall be given to Holders of Securities of this series not less than 10 days prior to such Special Record Date, or be paid at any time in any other lawful manner not inconsistent
with the requirements of any securities exchange on which the Securities of this series may be listed, and upon such notice as may be required by such exchange, all as more fully provided in said Indenture. 

Payment of the principal of (and premium, if any) and any such interest on this Security will be made at the office or agency of the Paying
Agent maintained for that purpose in London, Dublin or any financial center in a European Economic Area jurisdiction in Euro; provided, however, that at the option of the Company payment of interest may be made by check mailed to the address of the
Person entitled thereto as such address shall appear in the Security Register. If the Euro is unavailable to the Company due to the imposition of exchange controls or other circumstances beyond its control or the Euro is no longer used by the then
member states of the European Monetary Union that have adopted the Euro as their currency or for the settlement of transactions by public institutions of or within the international banking community, then all payments in respect of the 2032 Notes
will be made in U.S. Dollars until the Euro is again available to the Company or so used. In such circumstances, the amount payable on 

 
any date in Euro will be converted by the Company into U.S. Dollars at the rate mandated by the U.S. Federal Reserve Board as of the close of business on the second Business Day prior to the
relevant payment date or, in the event the U.S. Federal Reserve Board has not mandated a rate of conversion, on the basis of the most recent U.S. Dollar/Euro exchange rate published in The Wall Street Journal on or prior to the second Business Day
prior to the relevant payment date or, in the event The Wall Street Journal has not published such exchange rate, the rate will be determined in the Company’s sole discretion on the basis of the most recently available market exchange rate for
the Euro. For the avoidance of doubt, any such payment in respect of the 2032 Notes so made in U.S. Dollars will not constitute an Event of Default. Neither the Trustee nor the Paying Agent shall have any responsibility for any calculation or
conversion in connection with the foregoing. 
 Reference is hereby made to the further provisions of this Security set forth on the reverse
hereof, which further provisions shall for all purposes have the same effect as if set forth at this place. 
 Unless the certificate of
authentication hereon has been executed by the Trustee referred to on the reverse hereof by manual signature, this Security shall not be entitled to any benefit under the Indenture or be valid or obligatory for any purpose. 

 IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed under its
corporate seal. 
  

			
	MEDTRONIC GLOBAL HOLDINGS S.C.A., a Luxembourg corporate partnership limited by shares (société en commandite par actions) represented by Medtronic Global Holdings GP S.à.r.l. its General
Partner, in turn acting by

 
			
		
	By:	 	  

		 	Name:
		 	Title:

 Attest: 

 NOTATION OF GUARANTEE 

For value received, the undersigned (the “Guarantor”), to the extent set forth in and subject to the terms of the Indenture,
dated as of March 28, 2017 (the “Base Indenture”), among Medtronic Global Holdings S.C.A., a corporate partnership limited by shares (société en commandite par actions) incorporated and existing under the
laws of the Grand Duchy of Luxembourg (the “Company”), Medtronic Public Limited Company, a public limited company incorporated under the laws of Ireland (“Medtronic plc”), Medtronic, Inc., a Minnesota corporation
(“Medtronic, Inc.”), and Wells Fargo Bank, National Association, as Trustee (herein called the “Trustee”, which term includes any successor trustee under the Indenture (as defined below)), and as amended and
supplemented by the Fourth Supplemental Indenture, dated as of September 29, 2020 (the “Fourth Supplemental Indenture” and, together with the Base Indenture, the “Indenture”), among the Company, Medtronic plc,
Medtronic, Inc., the Trustee and Elavon Financial Services DAC, hereby fully and unconditionally guarantees, on a joint and several basis, to each Holder and to the Trustee and its successors and assigns, that the principal of and premium, if any,
and interest on the 2032 Notes shall be promptly paid in full when due, whether at Stated Maturity, by acceleration, redemption or otherwise, and interest on the overdue principal of and interest on the 2032 Notes, if any, if lawful, and all other
obligations of the Company to the Holders or the Trustee hereunder or thereunder shall be promptly paid in full or performed. 
 The
obligations of each Guarantor to the Holders and to the Trustee pursuant to this Notation of Guarantee and the Indenture are expressly set forth in Article 14 of the Indenture, and reference is hereby made to the Indenture for the precise terms and
limitations of this Notation of Guarantee. Each Holder of the 2032 Notes to which this Notation of Guarantee is endorsed, by accepting such 2032 Notes, agrees to and shall be bound by such provisions. 

All terms used in this Notation of Guarantee which are defined in the Indenture shall have the meanings assigned to them in the Indenture.

 IN WITNESS WHEREOF, each Guarantor has caused this Notation of Guarantee to be signed by a
duly authorized officer. 
 Dated:     , 20 

 

			
	MEDTRONIC PUBLIC LIMITED COMPANY

 
			
		
	By	 	  

 
			
	
	MEDTRONIC, INC.

 
			
		
	By	 	  

 This is one of the Securities of the series designated herein and referred to in the
within-mentioned Indenture. 
 Dated:      , 20 

 

			
	WELLS FARGO BANK, NATIONAL ASSOCIATION, Trustee

 
			
		
	By:	 	  

		 	Authorized Signatory

 (REVERSE OF SECURITY) 

MEDTRONIC GLOBAL HOLDINGS S.C.A. 

0.750% Senior Note Due 2032 

This Security is one of a duly authorized issue of securities of the Company (herein called the “Securities”), issued and to
be issued in one or more series under an Indenture, dated as of March 28, 2017 (the “Base Indenture”), among the Company, Medtronic Public Limited Company, a public limited company incorporated under the laws of Ireland
(“Medtronic plc”), Medtronic, Inc., a Minnesota corporation (“Medtronic, Inc.”), and Wells Fargo Bank, National Association, as Trustee (herein called the “Trustee”, which term includes any
successor trustee under the Indenture (as defined below)), and as amended and supplemented by the Fourth Supplemental Indenture, dated as of September 29, 2020 (the “Fourth Supplemental Indenture” and, together with the Base
Indenture, the “Indenture”), among the Company, Medtronic plc, Medtronic, Inc., the Trustee and Elavon Financial Services DAC, and reference is hereby made to the Indenture for a statement of the respective rights, limitations of
rights, duties and immunities thereunder of the Company, the Trustee and the Holders of the Securities and of the terms upon which the Securities are, and are to be, authenticated and delivered. This Security is one of the series designated on the
face hereof, initially limited in aggregate principal amount to €1,000,000,000. The Company may at any time issue additional Securities under the Indenture in unlimited amounts having the same terms as the Securities; provided that no
additional Securities may be issued if an Event of Default has occurred and is continuing with respect to the Securities. 
 The Securities
of this series may be redeemed at any time prior to the applicable Par Call Date, as a whole or in part, at the option of the Company, upon mailing notice of such redemption not less than 10 and not more than 60 days prior to the applicable
Redemption Date to the Holders of such Securities, at a Redemption Price equal to the greater of: 
 (i) 100% of the
principal amount of the Securities being redeemed; and 
 (ii) the sum, as determined by a Quotation Agent, of the present
values of the Remaining Scheduled Payments of principal and interest on the Securities to be redeemed (excluding any portion of such payments of interest accrued as of the Redemption Date and assuming that such Securities matured on the applicable
Par Call Date), discounted to the Redemption Date on an annual basis (ACTUAL/ACTUAL(ICMA)) at the Comparable Bond Rate, plus 20 basis points; 
 plus, in
each case, accrued and unpaid interest to, but not including, the Redemption Date. 
 In addition, at any time on and after the applicable
Par Call Date, the Securities are redeemable at the Company’s option, in whole or in part, at a Redemption Price equal to 100% of the principal amount of the Securities to be redeemed, plus accrued and unpaid interest, if any, to, but not
including, the Redemption Date. 

 In the event of redemption of this Security in part only, a new Security or Securities of
this series and of like tenor for the unredeemed portion hereof will be issued in the name of the Holder hereof upon the cancellation hereof. 

If an Event of Default with respect to Securities of this series shall occur and be continuing, the principal of the Securities of this series
may be declared due and payable in the manner and with the effect provided in the Indenture. 
 The Indenture permits, with certain
exceptions as therein provided, the amendment thereof and the modification of the rights and obligations of the Company and the rights of the Holders of the Securities of each series to be affected under the Indenture at any time by the Company and
the Trustee with the consent of the Holders of a majority in principal amount of the Securities at the time Outstanding of each series to be affected. The Indenture also contains provisions permitting the Holders of specified percentages in
principal amount of the Securities of each series at the time Outstanding, on behalf of the Holders of all Securities of such series, to waive compliance by the Company with certain provisions of the Indenture and certain past defaults under the
Indenture and their consequences. Any such consent or waiver by the Holder of this Security shall be conclusive and binding upon such Holder and upon all future Holders of this Security and of any Security issued upon the registration of transfer
hereof or in exchange herefor or in lieu hereof, whether or not notation of such consent or waiver is made upon this Security. 
 As
provided in and subject to the provisions of the Indenture, the Holder of this Security shall not have the right to institute any proceeding with respect to the Indenture or for the appointment of a receiver or trustee or for any other remedy
thereunder, unless such Holder shall have previously given the Trustee written notice of a continuing Event of Default with respect to the Securities of this series, the Holders of not less than 25% in principal amount of the Securities of this
series at the time Outstanding shall have made written request to the Trustee to institute proceedings in respect of such Event of Default as Trustee and offered the Trustee indemnity against the costs, expenses and liabilities to be incurred in
compliance with such request, and the Trustee shall not have received from the Holders of a majority in principal amount of Securities of this series at the time Outstanding a direction inconsistent with such request, and shall have failed to
institute any such proceeding, for 60 days after receipt of such notice, request and offer of indemnity. The foregoing shall not apply to any suit instituted by the Holder of this Security for the enforcement of any payment of principal hereof or
any premium or interest hereon on or after the respective due dates expressed herein. 
 As provided in the Indenture and subject to certain
limitations therein set forth, the transfer of this Security is registrable in the Security Register, upon surrender of this Security for registration of transfer at the office or agency of the Company in any place where the principal of and any
premium and interest on this Security are payable, duly endorsed by, or accompanied by a written instrument of transfer in form satisfactory to the Company and the Security Registrar duly executed by, the Holder hereof or the Holder’s attorney
duly authorized in writing, and thereupon one or more new Securities of this series and of like tenor, of authorized denominations and for the same aggregate principal amount, will be issued to the designated transferee or transferees. 

 The Securities of this series are issuable only in registered form without coupons in
denominations of €100,000 or an integral multiple of €1,000 in excess thereof. As provided in the Indenture and subject to certain limitations therein set forth, Securities of this series are exchangeable for a like aggregate principal
amount of Securities of this series and of like tenor of a different authorized denomination, as requested by the Holder surrendering the same. 

No service charge shall be made to a Holder for any such registration of transfer or exchange, but the Company may require payment of a sum
sufficient to cover any tax or other governmental charge payable in connection therewith. 
 Prior to due presentment of this Security for
registration of transfer, the Company, the Trustee and any agent of the Company or the Trustee may treat the Person in whose name this Security is registered as the owner hereof for all purposes, whether or not this Security be overdue, and neither
the Company, the Trustee nor any such agent shall be affected by notice to the contrary. 
 Reference is made to the Indenture. Such further
provisions shall for all purposes have the same effect as though fully set forth herein. 
 All terms used in this Security which are
defined in the Indenture shall have the meanings assigned to them in the Indenture. 

 EXHIBIT E 

FORM OF NOTE 
 THIS
SECURITY IS A GLOBAL SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF A DEPOSITARY OR A NOMINEE THEREOF. THIS SECURITY MAY NOT BE EXCHANGED IN WHOLE OR IN PART FOR A SECURITY REGISTERED, AND NO
TRANSFER OF THIS SECURITY IN WHOLE OR IN PART MAY BE REGISTERED, IN THE NAME OF ANY PERSON OTHER THAN SUCH DEPOSITARY OR A NOMINEE THEREOF, EXCEPT IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE. 

UNLESS THIS CERTIFICATE IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF EUROCLEAR BANK SA/NV (“EUROCLEAR”) AND CLEARSTREAM BANKING,
S.A. (“CLEARSTREAM” AND, TOGETHER WITH EUROCLEAR, “EUROCLEAR/CLEARSTREAM”), TO THE COMPANY OR ITS AGENT FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF USB NOMINEES (UK)
LIMITED OR IN SUCH OTHER NAME AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF EUROCLEAR/CLEARSTREAM (AND ANY PAYMENT IS MADE TO USB NOMINEES (UK) LIMITED OR TO SUCH OTHER ENTITY AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF
EUROCLEAR/CLEARSTREAM), ANY TRANSFER, PLEDGE OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL INASMUCH AS THE REGISTERED OWNER HEREOF, ELAVON FINANCIAL SERVICES DAC, HAS AN INTEREST HEREIN. TRANSFERS OF THIS GLOBAL SECURITY
SHALL BE LIMITED TO TRANSFERS IN WHOLE, BUT NOT IN PART, TO NOMINEES OF USB NOMINEES (UK) LIMITED OR TO A SUCCESSOR THEREOF OR SUCH SUCCESSOR’S NOMINEE. 

 MEDTRONIC GLOBAL HOLDINGS S.C.A. 

1.375% Senior Note Due 2040 
  

			
		  	CUSIP No.: 58507L AV1
	 No.
	  	    ISIN No.: XS2238792332
		  	COMMON CODE: 223879233
		  	€            

 Medtronic Global Holdings S.C.A., a corporate partnership limited by shares (société en
commandite par actions) incorporated and existing under the laws of the Grand Duchy of Luxembourg (herein called the “Company”, which term includes any successor corporation under the Indenture hereinafter referred to), for
value received, hereby promises to pay to USB Nominees (UK) Limited or registered assigns, the principal sum of      Euros on October 15, 2040 and to pay interest thereon from September 29, 2020 or from the most recent
Interest Payment Date to which interest has been paid or duly provided for, annually in arrears on October 15 in each year, commencing October 15, 2021, at the rate of 1.375% per annum, until the principal hereof is paid or made available
for payment. The Company shall pay interest on overdue principal, and on overdue installments of interest (without regard to any applicable grace periods) to the extent lawful, from time to time on demand at the rate borne by this Security. 

The interest so payable, and punctually paid or duly provided for, on any Interest Payment Date will, as provided in such Indenture, be paid
to the Person in whose name this Security is registered at the close of business on the Regular Record Date for such interest, which shall be the Business Day immediately preceding such Interest Payment Date. Any such interest not so punctually paid
or duly provided for will forthwith cease to be payable to the Holder on such Regular Record Date and may either be paid to the Person in whose name this Security is registered at the close of business on a Special Record Date for the payment of
such Defaulted Interest to be fixed by the Trustee, notice whereof shall be given to Holders of Securities of this series not less than 10 days prior to such Special Record Date, or be paid at any time in any other lawful manner not inconsistent
with the requirements of any securities exchange on which the Securities of this series may be listed, and upon such notice as may be required by such exchange, all as more fully provided in said Indenture. 

Payment of the principal of (and premium, if any) and any such interest on this Security will be made at the office or agency of the Paying
Agent maintained for that purpose in London, Dublin or any financial center in a European Economic Area jurisdiction in Euro; provided, however, that at the option of the Company payment of interest may be made by check mailed to the address of the
Person entitled thereto as such address shall appear in the Security Register. If the Euro is unavailable to the Company due to the imposition of exchange controls or other circumstances beyond its control or the Euro is no longer used by the then
member states of the European Monetary Union that have adopted the Euro as their currency or for the settlement of transactions by public institutions of or within the international banking community, then all payments in respect of the 2040 Notes
will be made in U.S. Dollars until the Euro is again available to the Company or so used. In such circumstances, the amount payable on 

 
any date in Euro will be converted by the Company into U.S. Dollars at the rate mandated by the U.S. Federal Reserve Board as of the close of business on the second Business Day prior to the
relevant payment date or, in the event the U.S. Federal Reserve Board has not mandated a rate of conversion, on the basis of the most recent U.S. Dollar/Euro exchange rate published in The Wall Street Journal on or prior to the second Business Day
prior to the relevant payment date or, in the event The Wall Street Journal has not published such exchange rate, the rate will be determined in the Company’s sole discretion on the basis of the most recently available market exchange rate for
the Euro. For the avoidance of doubt, any such payment in respect of the 2040 Notes so made in U.S. Dollars will not constitute an Event of Default. Neither the Trustee nor the Paying Agent shall have any responsibility for any calculation or
conversion in connection with the foregoing. 
 Reference is hereby made to the further provisions of this Security set forth on the reverse
hereof, which further provisions shall for all purposes have the same effect as if set forth at this place. 
 Unless the certificate of
authentication hereon has been executed by the Trustee referred to on the reverse hereof by manual signature, this Security shall not be entitled to any benefit under the Indenture or be valid or obligatory for any purpose. 

 IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed under its
corporate seal. 
  

			
	MEDTRONIC GLOBAL HOLDINGS S.C.A., a Luxembourg corporate partnership limited by shares (société en commandite par actions) represented by Medtronic Global Holdings GP S.à.r.l. its General
Partner, in turn acting by

 
			
		
	By:	 	  

		 	Name:
		 	Title:

 Attest: 

 NOTATION OF GUARANTEE 

For value received, the undersigned (the “Guarantor”), to the extent set forth in and subject to the terms of the Indenture,
dated as of March 28, 2017 (the “Base Indenture”), among Medtronic Global Holdings S.C.A., a corporate partnership limited by shares (société en commandite par actions) incorporated and existing under the
laws of the Grand Duchy of Luxembourg (the “Company”), Medtronic Public Limited Company, a public limited company incorporated under the laws of Ireland (“Medtronic plc”), Medtronic, Inc., a Minnesota corporation
(“Medtronic, Inc.”), and Wells Fargo Bank, National Association, as Trustee (herein called the “Trustee”, which term includes any successor trustee under the Indenture (as defined below)), and as amended and
supplemented by the Fourth Supplemental Indenture, dated as of September 29, 2020 (the “Fourth Supplemental Indenture” and, together with the Base Indenture, the “Indenture”), among the Company, Medtronic plc,
Medtronic, Inc., the Trustee and Elavon Financial Services DAC, hereby fully and unconditionally guarantees, on a joint and several basis, to each Holder and to the Trustee and its successors and assigns, that the principal of and premium, if any,
and interest on the 2040 Notes shall be promptly paid in full when due, whether at Stated Maturity, by acceleration, redemption or otherwise, and interest on the overdue principal of and interest on the 2040 Notes, if any, if lawful, and all other
obligations of the Company to the Holders or the Trustee hereunder or thereunder shall be promptly paid in full or performed. 
 The
obligations of each Guarantor to the Holders and to the Trustee pursuant to this Notation of Guarantee and the Indenture are expressly set forth in Article 14 of the Indenture, and reference is hereby made to the Indenture for the precise terms and
limitations of this Notation of Guarantee. Each Holder of the 2040 Notes to which this Notation of Guarantee is endorsed, by accepting such 2040 Notes, agrees to and shall be bound by such provisions. 

All terms used in this Notation of Guarantee which are defined in the Indenture shall have the meanings assigned to them in the Indenture.

 IN WITNESS WHEREOF, each Guarantor has caused this Notation of Guarantee to be signed by a
duly authorized officer. 
 Dated:    , 20 

 

			
	 MEDTRONIC PUBLIC LIMITED
COMPANY

 
			
		
	 By
	 	
 

			
	
	 MEDTRONIC, INC.

			
		
	 By
	 	  

 This is one of the Securities of the series designated herein and referred to in the
within-mentioned Indenture. 
 Dated:      , 20 

 

			
	WELLS FARGO BANK, NATIONAL ASSOCIATION, Trustee

 
			
		
	By:	 	  

		 	Authorized Signatory

 (REVERSE OF SECURITY) 

MEDTRONIC GLOBAL HOLDINGS S.C.A. 

1.375% Senior Note Due 2040 

This Security is one of a duly authorized issue of securities of the Company (herein called the “Securities”), issued and to
be issued in one or more series under an Indenture, dated as of March 28, 2017 (the “Base Indenture”), among the Company, Medtronic Public Limited Company, a public limited company incorporated under the laws of Ireland
(“Medtronic plc”), Medtronic, Inc., a Minnesota corporation (“Medtronic, Inc.”), and Wells Fargo Bank, National Association, as Trustee (herein called the “Trustee”, which term includes any
successor trustee under the Indenture (as defined below)), and as amended and supplemented by the Fourth Supplemental Indenture, dated as of September 29, 2020 (the “Fourth Supplemental Indenture” and, together with the Base
Indenture, the “Indenture”), among the Company, Medtronic plc, Medtronic, Inc., the Trustee and Elavon Financial Services DAC, and reference is hereby made to the Indenture for a statement of the respective rights, limitations of
rights, duties and immunities thereunder of the Company, the Trustee and the Holders of the Securities and of the terms upon which the Securities are, and are to be, authenticated and delivered. This Security is one of the series designated on the
face hereof, initially limited in aggregate principal amount to €1,000,000,000. The Company may at any time issue additional Securities under the Indenture in unlimited amounts having the same terms as the Securities; provided that no
additional Securities may be issued if an Event of Default has occurred and is continuing with respect to the Securities. 
 The Securities
of this series may be redeemed at any time prior to the applicable Par Call Date, as a whole or in part, at the option of the Company, upon mailing notice of such redemption not less than 10 and not more than 60 days prior to the applicable
Redemption Date to the Holders of such Securities, at a Redemption Price equal to the greater of: 
 (i) 100% of the
principal amount of the Securities being redeemed; and 
 (ii) the sum, as determined by a Quotation Agent, of the present
values of the Remaining Scheduled Payments of principal and interest on the Securities to be redeemed (excluding any portion of such payments of interest accrued as of the Redemption Date and assuming that such Securities matured on the applicable
Par Call Date), discounted to the Redemption Date on an annual basis (ACTUAL/ACTUAL(ICMA)) at the Comparable Bond Rate, plus 30 basis points; 
 plus, in
each case, accrued and unpaid interest to, but not including, the Redemption Date. 
 In addition, at any time on and after the applicable
Par Call Date, the Securities are redeemable at the Company’s option, in whole or in part, at a Redemption Price equal to 100% of the principal amount of the Securities to be redeemed, plus accrued and unpaid interest, if any, to, but not
including, the Redemption Date. 

 In the event of redemption of this Security in part only, a new Security or Securities of
this series and of like tenor for the unredeemed portion hereof will be issued in the name of the Holder hereof upon the cancellation hereof. 

If an Event of Default with respect to Securities of this series shall occur and be continuing, the principal of the Securities of this series
may be declared due and payable in the manner and with the effect provided in the Indenture. 
 The Indenture permits, with certain
exceptions as therein provided, the amendment thereof and the modification of the rights and obligations of the Company and the rights of the Holders of the Securities of each series to be affected under the Indenture at any time by the Company and
the Trustee with the consent of the Holders of a majority in principal amount of the Securities at the time Outstanding of each series to be affected. The Indenture also contains provisions permitting the Holders of specified percentages in
principal amount of the Securities of each series at the time Outstanding, on behalf of the Holders of all Securities of such series, to waive compliance by the Company with certain provisions of the Indenture and certain past defaults under the
Indenture and their consequences. Any such consent or waiver by the Holder of this Security shall be conclusive and binding upon such Holder and upon all future Holders of this Security and of any Security issued upon the registration of transfer
hereof or in exchange herefor or in lieu hereof, whether or not notation of such consent or waiver is made upon this Security. 
 As
provided in and subject to the provisions of the Indenture, the Holder of this Security shall not have the right to institute any proceeding with respect to the Indenture or for the appointment of a receiver or trustee or for any other remedy
thereunder, unless such Holder shall have previously given the Trustee written notice of a continuing Event of Default with respect to the Securities of this series, the Holders of not less than 25% in principal amount of the Securities of this
series at the time Outstanding shall have made written request to the Trustee to institute proceedings in respect of such Event of Default as Trustee and offered the Trustee indemnity against the costs, expenses and liabilities to be incurred in
compliance with such request, and the Trustee shall not have received from the Holders of a majority in principal amount of Securities of this series at the time Outstanding a direction inconsistent with such request, and shall have failed to
institute any such proceeding, for 60 days after receipt of such notice, request and offer of indemnity. The foregoing shall not apply to any suit instituted by the Holder of this Security for the enforcement of any payment of principal hereof or
any premium or interest hereon on or after the respective due dates expressed herein. 
 As provided in the Indenture and subject to certain
limitations therein set forth, the transfer of this Security is registrable in the Security Register, upon surrender of this Security for registration of transfer at the office or agency of the Company in any place where the principal of and any
premium and interest on this Security are payable, duly endorsed by, or accompanied by a written instrument of transfer in form satisfactory to the Company and the Security Registrar duly executed by, the Holder hereof or the Holder’s attorney
duly authorized in writing, and thereupon one or more new Securities of this series and of like tenor, of authorized denominations and for the same aggregate principal amount, will be issued to the designated transferee or transferees. 

 The Securities of this series are issuable only in registered form without coupons in
denominations of €100,000 or an integral multiple of €1,000 in excess thereof. As provided in the Indenture and subject to certain limitations therein set forth, Securities of this series are exchangeable for a like aggregate principal
amount of Securities of this series and of like tenor of a different authorized denomination, as requested by the Holder surrendering the same. 

No service charge shall be made to a Holder for any such registration of transfer or exchange, but the Company may require payment of a sum
sufficient to cover any tax or other governmental charge payable in connection therewith. 
 Prior to due presentment of this Security for
registration of transfer, the Company, the Trustee and any agent of the Company or the Trustee may treat the Person in whose name this Security is registered as the owner hereof for all purposes, whether or not this Security be overdue, and neither
the Company, the Trustee nor any such agent shall be affected by notice to the contrary. 
 Reference is made to the Indenture. Such further
provisions shall for all purposes have the same effect as though fully set forth herein. 
 All terms used in this Security which are
defined in the Indenture shall have the meanings assigned to them in the Indenture. 

 EXHIBIT F 

FORM OF NOTE 
 THIS
SECURITY IS A GLOBAL SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF A DEPOSITARY OR A NOMINEE THEREOF. THIS SECURITY MAY NOT BE EXCHANGED IN WHOLE OR IN PART FOR A SECURITY REGISTERED, AND NO
TRANSFER OF THIS SECURITY IN WHOLE OR IN PART MAY BE REGISTERED, IN THE NAME OF ANY PERSON OTHER THAN SUCH DEPOSITARY OR A NOMINEE THEREOF, EXCEPT IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE. 

UNLESS THIS CERTIFICATE IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF EUROCLEAR BANK SA/NV (“EUROCLEAR”) AND CLEARSTREAM BANKING,
S.A. (“CLEARSTREAM” AND, TOGETHER WITH EUROCLEAR, “EUROCLEAR/CLEARSTREAM”), TO THE COMPANY OR ITS AGENT FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF USB NOMINEES (UK)
LIMITED OR IN SUCH OTHER NAME AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF EUROCLEAR/CLEARSTREAM (AND ANY PAYMENT IS MADE TO USB NOMINEES (UK) LIMITED OR TO SUCH OTHER ENTITY AS IS REQUESTED BY AN AUTHORIZED REPRESENTATIVE OF
EUROCLEAR/CLEARSTREAM), ANY TRANSFER, PLEDGE OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL INASMUCH AS THE REGISTERED OWNER HEREOF, ELAVON FINANCIAL SERVICES DAC, HAS AN INTEREST HEREIN. TRANSFERS OF THIS GLOBAL SECURITY
SHALL BE LIMITED TO TRANSFERS IN WHOLE, BUT NOT IN PART, TO NOMINEES OF USB NOMINEES (UK) LIMITED OR TO A SUCCESSOR THEREOF OR SUCH SUCCESSOR’S NOMINEE. 

 MEDTRONIC GLOBAL HOLDINGS S.C.A. 

1.625% Senior Note Due 2050 
  

			
		  	CUSIP No.: 58507L AW9
	 No.
	  	    ISIN No.: XS2238792688
		  	COMMON CODE: 223879268
		  	€            

 Medtronic Global Holdings S.C.A., a corporate partnership limited by shares (société en
commandite par actions) incorporated and existing under the laws of the Grand Duchy of Luxembourg (herein called the “Company”, which term includes any successor corporation under the Indenture hereinafter referred to), for
value received, hereby promises to pay to USB Nominees (UK) Limited or registered assigns, the principal sum of      Euros on October 15, 2050 and to pay interest thereon from September 29, 2020 or from the most recent
Interest Payment Date to which interest has been paid or duly provided for, annually in arrears on October 15 in each year, commencing October 15, 2021, at the rate of 1.625% per annum, until the principal hereof is paid or made available
for payment. The Company shall pay interest on overdue principal, and on overdue installments of interest (without regard to any applicable grace periods) to the extent lawful, from time to time on demand at the rate borne by this Security. 

The interest so payable, and punctually paid or duly provided for, on any Interest Payment Date will, as provided in such Indenture, be paid
to the Person in whose name this Security is registered at the close of business on the Regular Record Date for such interest, which shall be the Business Day immediately preceding such Interest Payment Date. Any such interest not so punctually paid
or duly provided for will forthwith cease to be payable to the Holder on such Regular Record Date and may either be paid to the Person in whose name this Security is registered at the close of business on a Special Record Date for the payment of
such Defaulted Interest to be fixed by the Trustee, notice whereof shall be given to Holders of Securities of this series not less than 10 days prior to such Special Record Date, or be paid at any time in any other lawful manner not inconsistent
with the requirements of any securities exchange on which the Securities of this series may be listed, and upon such notice as may be required by such exchange, all as more fully provided in said Indenture. 

Payment of the principal of (and premium, if any) and any such interest on this Security will be made at the office or agency of the Paying
Agent maintained for that purpose in London, Dublin or any financial center in a European Economic Area jurisdiction in Euro; provided, however, that at the option of the Company payment of interest may be made by check mailed to the address of the
Person entitled thereto as such address shall appear in the Security Register. If the Euro is unavailable to the Company due to the imposition of exchange controls or other circumstances beyond its control or the Euro is no longer used by the then
member states of the European Monetary Union that have adopted the Euro as their currency or for the settlement of transactions by public institutions of or within the international banking community, then all payments in respect of the 2050 Notes
will be made in U.S. Dollars until the Euro is again available to the Company or so used. In such circumstances, the amount payable on 

 
any date in Euro will be converted by the Company into U.S. Dollars at the rate mandated by the U.S. Federal Reserve Board as of the close of business on the second Business Day prior to the
relevant payment date or, in the event the U.S. Federal Reserve Board has not mandated a rate of conversion, on the basis of the most recent U.S. Dollar/Euro exchange rate published in The Wall Street Journal on or prior to the second Business Day
prior to the relevant payment date or, in the event The Wall Street Journal has not published such exchange rate, the rate will be determined in the Company’s sole discretion on the basis of the most recently available market exchange rate for
the Euro. For the avoidance of doubt, any such payment in respect of the 2050 Notes so made in U.S. Dollars will not constitute an Event of Default. Neither the Trustee nor the Paying Agent shall have any responsibility for any calculation or
conversion in connection with the foregoing. 
 Reference is hereby made to the further provisions of this Security set forth on the reverse
hereof, which further provisions shall for all purposes have the same effect as if set forth at this place. 
 Unless the certificate of
authentication hereon has been executed by the Trustee referred to on the reverse hereof by manual signature, this Security shall not be entitled to any benefit under the Indenture or be valid or obligatory for any purpose. 

 IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed under its
corporate seal. 
  

			
	MEDTRONIC GLOBAL HOLDINGS S.C.A., a Luxembourg corporate partnership limited by shares (société en commandite par actions) represented by Medtronic Global Holdings GP S.à.r.l. its General
Partner, in turn acting by

 
			
		
	By:	 	  

		 	Name:
		 	Title:

 Attest: 

 NOTATION OF GUARANTEE 

For value received, the undersigned (the “Guarantor”), to the extent set forth in and subject to the terms of the Indenture,
dated as of March 28, 2017 (the “Base Indenture”), among Medtronic Global Holdings S.C.A., a corporate partnership limited by shares (société en commandite par actions) incorporated and existing under the
laws of the Grand Duchy of Luxembourg (the “Company”), Medtronic Public Limited Company, a public limited company incorporated under the laws of Ireland (“Medtronic plc”), Medtronic, Inc., a Minnesota corporation
(“Medtronic, Inc.”), and Wells Fargo Bank, National Association, as Trustee (herein called the “Trustee”, which term includes any successor trustee under the Indenture (as defined below)), and as amended and
supplemented by the Fourth Supplemental Indenture, dated as of September 29, 2020 (the “Fourth Supplemental Indenture” and, together with the Base Indenture, the “Indenture”), among the Company, Medtronic plc,
Medtronic, Inc., the Trustee and Elavon Financial Services DAC, hereby fully and unconditionally guarantees, on a joint and several basis, to each Holder and to the Trustee and its successors and assigns, that the principal of and premium, if any,
and interest on the 2050 Notes shall be promptly paid in full when due, whether at Stated Maturity, by acceleration, redemption or otherwise, and interest on the overdue principal of and interest on the 2050 Notes, if any, if lawful, and all other
obligations of the Company to the Holders or the Trustee hereunder or thereunder shall be promptly paid in full or performed. 
 The
obligations of each Guarantor to the Holders and to the Trustee pursuant to this Notation of Guarantee and the Indenture are expressly set forth in Article 14 of the Indenture, and reference is hereby made to the Indenture for the precise terms and
limitations of this Notation of Guarantee. Each Holder of the 2050 Notes to which this Notation of Guarantee is endorsed, by accepting such 2050 Notes, agrees to and shall be bound by such provisions. 

All terms used in this Notation of Guarantee which are defined in the Indenture shall have the meanings assigned to them in the Indenture.

 IN WITNESS WHEREOF, each Guarantor has caused this Notation of Guarantee to be signed by a
duly authorized officer. 
 Dated:    , 20 

 

			
	MEDTRONIC PUBLIC LIMITED COMPANY

 
			
		
	By	 	  

 
			
	
	MEDTRONIC, INC.

 
			
		
	By	 	  

 This is one of the Securities of the series designated herein and referred to in the
within-mentioned Indenture. 
 Dated:      , 20 

 

			
	WELLS FARGO BANK, NATIONAL ASSOCIATION, Trustee

 
			
		
	By:	 	  

		 	Authorized Signatory

 (REVERSE OF SECURITY) 

MEDTRONIC GLOBAL HOLDINGS S.C.A. 

1.625% Senior Note Due 2050 

This Security is one of a duly authorized issue of securities of the Company (herein called the “Securities”), issued and to
be issued in one or more series under an Indenture, dated as of March 28, 2017 (the “Base Indenture”), among the Company, Medtronic Public Limited Company, a public limited company incorporated under the laws of Ireland
(“Medtronic plc”), Medtronic, Inc., a Minnesota corporation (“Medtronic, Inc.”), and Wells Fargo Bank, National Association, as Trustee (herein called the “Trustee”, which term includes any
successor trustee under the Indenture (as defined below)), and as amended and supplemented by the Fourth Supplemental Indenture, dated as of September 29, 2020 (the “Fourth Supplemental Indenture” and, together with the Base
Indenture, the “Indenture”), among the Company, Medtronic plc, Medtronic, Inc., the Trustee and Elavon Financial Services DAC, and reference is hereby made to the Indenture for a statement of the respective rights, limitations of
rights, duties and immunities thereunder of the Company, the Trustee and the Holders of the Securities and of the terms upon which the Securities are, and are to be, authenticated and delivered. This Security is one of the series designated on the
face hereof, initially limited in aggregate principal amount to €1,000,000,000. The Company may at any time issue additional Securities under the Indenture in unlimited amounts having the same terms as the Securities; provided that no
additional Securities may be issued if an Event of Default has occurred and is continuing with respect to the Securities. 
 The Securities
of this series may be redeemed at any time prior to the applicable Par Call Date, as a whole or in part, at the option of the Company, upon mailing notice of such redemption not less than 10 and not more than 60 days prior to the applicable
Redemption Date to the Holders of such Securities, at a Redemption Price equal to the greater of: 
 (i) 100% of the
principal amount of the Securities being redeemed; and 
 (ii) the sum, as determined by a Quotation Agent, of the present
values of the Remaining Scheduled Payments of principal and interest on the Securities to be redeemed (excluding any portion of such payments of interest accrued as of the Redemption Date and assuming that such Securities matured on the applicable
Par Call Date), discounted to the Redemption Date on an annual basis (ACTUAL/ACTUAL(ICMA)) at the Comparable Bond Rate, plus 30 basis points; 
 plus, in
each case, accrued and unpaid interest to, but not including, the Redemption Date. 
 In addition, at any time on and after the applicable
Par Call Date, the Securities are redeemable at the Company’s option, in whole or in part, at a Redemption Price equal to 100% of the principal amount of the Securities to be redeemed, plus accrued and unpaid interest, if any, to, but not
including, the Redemption Date. 

 In the event of redemption of this Security in part only, a new Security or Securities of
this series and of like tenor for the unredeemed portion hereof will be issued in the name of the Holder hereof upon the cancellation hereof. 

If an Event of Default with respect to Securities of this series shall occur and be continuing, the principal of the Securities of this series
may be declared due and payable in the manner and with the effect provided in the Indenture. 
 The Indenture permits, with certain
exceptions as therein provided, the amendment thereof and the modification of the rights and obligations of the Company and the rights of the Holders of the Securities of each series to be affected under the Indenture at any time by the Company and
the Trustee with the consent of the Holders of a majority in principal amount of the Securities at the time Outstanding of each series to be affected. The Indenture also contains provisions permitting the Holders of specified percentages in
principal amount of the Securities of each series at the time Outstanding, on behalf of the Holders of all Securities of such series, to waive compliance by the Company with certain provisions of the Indenture and certain past defaults under the
Indenture and their consequences. Any such consent or waiver by the Holder of this Security shall be conclusive and binding upon such Holder and upon all future Holders of this Security and of any Security issued upon the registration of transfer
hereof or in exchange herefor or in lieu hereof, whether or not notation of such consent or waiver is made upon this Security. 
 As
provided in and subject to the provisions of the Indenture, the Holder of this Security shall not have the right to institute any proceeding with respect to the Indenture or for the appointment of a receiver or trustee or for any other remedy
thereunder, unless such Holder shall have previously given the Trustee written notice of a continuing Event of Default with respect to the Securities of this series, the Holders of not less than 25% in principal amount of the Securities of this
series at the time Outstanding shall have made written request to the Trustee to institute proceedings in respect of such Event of Default as Trustee and offered the Trustee indemnity against the costs, expenses and liabilities to be incurred in
compliance with such request, and the Trustee shall not have received from the Holders of a majority in principal amount of Securities of this series at the time Outstanding a direction inconsistent with such request, and shall have failed to
institute any such proceeding, for 60 days after receipt of such notice, request and offer of indemnity. The foregoing shall not apply to any suit instituted by the Holder of this Security for the enforcement of any payment of principal hereof or
any premium or interest hereon on or after the respective due dates expressed herein. 
 As provided in the Indenture and subject to certain
limitations therein set forth, the transfer of this Security is registrable in the Security Register, upon surrender of this Security for registration of transfer at the office or agency of the Company in any place where the principal of and any
premium and interest on this Security are payable, duly endorsed by, or accompanied by a written instrument of transfer in form satisfactory to the Company and the Security Registrar duly executed by, the Holder hereof or the Holder’s attorney
duly authorized in writing, and thereupon one or more new Securities of this series and of like tenor, of authorized denominations and for the same aggregate principal amount, will be issued to the designated transferee or transferees. 

 The Securities of this series are issuable only in registered form without coupons in
denominations of €100,000 or an integral multiple of €1,000 in excess thereof. As provided in the Indenture and subject to certain limitations therein set forth, Securities of this series are exchangeable for a like aggregate principal
amount of Securities of this series and of like tenor of a different authorized denomination, as requested by the Holder surrendering the same. 

No service charge shall be made to a Holder for any such registration of transfer or exchange, but the Company may require payment of a sum
sufficient to cover any tax or other governmental charge payable in connection therewith. 
 Prior to due presentment of this Security for
registration of transfer, the Company, the Trustee and any agent of the Company or the Trustee may treat the Person in whose name this Security is registered as the owner hereof for all purposes, whether or not this Security be overdue, and neither
the Company, the Trustee nor any such agent shall be affected by notice to the contrary. 
 Reference is made to the Indenture. Such further
provisions shall for all purposes have the same effect as though fully set forth herein. 
 All terms used in this Security which are
defined in the Indenture shall have the meanings assigned to them in the Indenture.

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