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                                                                    EXHIBIT 10.1

                                SECOND AMENDMENT
                                       TO
                         TRIANGLE PHARMACEUTICALS, INC.
                            1996 STOCK INCENTIVE PLAN
                (AS AMENDED AND RESTATED THROUGH MARCH 27, 1998)

     THIS SECOND AMENDMENT is made and entered into this 23rd day of May, 2002,
effective as stated below, by Triangle Pharmaceuticals, Inc., a Delaware
corporation (the "Corporation").

                              W I T N E S S E T H:

     WHEREAS, the Corporation has previously adopted the Triangle
Pharmaceuticals, Inc. 1996 Stock Incentive Plan, as last amended through May 18,
2001 ("Plan");

     WHEREAS, Article Six, Section IV, of the Plan provides, in part, that the
Board of Directors of the Corporation (the "Board") shall have complete and
exclusive power and authority to amend or modify the Plan in any or all
respects, subject to stockholder approval if required by applicable laws or
regulations or otherwise required by the Board;

     WHEREAS, on February 27, 2002, the Board authorized the following
amendments to the Plan, subject to the approval of the stockholders of the
Corporation at the 2002 annual meeting of the Corporation:

     1.   the number of shares of common stock authorized for issuance pursuant
          to the 1996 Incentive Plan will be increased by 1,962,329 shares, so
          that the number of shares available for new grants in 2002 will be
          3,500,000 shares as of February 27, 2002; and

     2.   for each of the years 2003 through 2006, the number of shares of
          common stock authorized for issuance pursuant to the 1996 Incentive
          Plan will increase on each January 1 by the lesser of 4.5% of the
          total number of shares of Triangle common stock outstanding on the
          immediately preceding December 31 or 5,000,000 shares.

     WHEREAS, on May 23, 2002 the stockholders of the Corporation approved such
amendments at the 2002 annual meeting of the Corporation.

     NOW, THEREFORE, the Corporation hereby amends the Plan as follows:

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I.   The following hereby amends and restates in its entirely Article One,
Section V.A of the Plan:

          "The stock issuable under the Plan shall be shares of authorized but
     unissued or reacquired Common Stock, including shares repurchased by the
     Corporation on the open market. Effective February 27, 2002, the number of
     shares of Common Stock reserved for issuance under the Plan shall be
     9,162,158 shares. On January 1 of each year, beginning January 1, 2003, the
     number of shares of Common Stock reserved for issuance under the Plan shall
     automatically increase so that the number of authorized shares available
     for new grants under the plan on each January 1 will equal the lesser of
     4.5% of the total number of shares of Triangle Common Stock outstanding on
     the preceding December 31st or 5,000,000 shares. For example, if on any
     such December 31, there are 200,000 shares that remain available for future
     grants under the Plan, and 70,000,000 shares of Common Stock are
     outstanding, then the number of shares issuable under the Plan shall be
     increased by 2,950,000 additional shares, so that 3,150,000 shares
     (70,000,000 x 4.5%) are available for issuance under the Plan as of the
     following January 1."

III. The following hereby amends and restates in its entirety Article Six,
Section 3.D of the Plan:

          "D. On the Plan Effective Date, 2,200,000 shares of Common Stock were
     available for issuance over the term of the Plan. Such authorized share
     reserve was comprised of the number of shares which remained available for
     issuance, as of the Plan Effective Date, under the Predecessor Plan as last
     approved by the Corporation's stockholders, including the shares subject to
     the outstanding options incorporated into the Plan and the additional
     shares which were otherwise available for future grant, plus an additional
     increase of 500,000 shares authorized by the Board and subsequently
     approved by the stockholders prior to the Section 12 Registration Date.

          On December 4, 1997, the Board adopted an amendment to the Plan (the
     "1997 Amendment") to effect the following changes: (i) increase the maximum
     number of shares of Common Stock available for issuance over the term of
     the Plan by an additional 1,000,000 shares, and (ii) implement an automatic
     share increase feature pursuant to which the number of shares of Common
     Stock available for issuance under the Plan automatically increased on
     January 1 of each of the calendar years 1999, 2000 and 2001 by an amount
     equal to four percent (4%) of the total number of shares of Common Stock
     issued and outstanding on December 31st of the immediately preceding
     calendar year; provided, however, that in no event did any such annual
     increase exceed the difference between (x) 1,000,000 shares and (y) the
     number of shares of Common Stock available for future option grants under
     the Plan on such December 31 (net of all outstanding options and unvested
     stock issuances). The increase under this provision was 629,723 shares
     effective January 1, 1999, 905,791 shares effective January 1,

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     2000, and 964,315 shares effective January 1, 2001, for an aggregate of
     2,499,829 over this three year period.

          In addition, on March 27, 1998, the Board adopted an amendment to the
     Plan (the "1998 Amendment") to effect the following change: under the
     Automatic Option Grant Program, effective with the 1998 Annual Meeting (A)
     automatically grant to each individual who is first appointed or elected as
     a non-employee Board member an option to purchase shares of Common Stock in
     an amount equal to 2,000 shares of Common Stock plus 2,000 shares for any
     partial year and for each full year of the term for which the non-employee
     Board member is first appointed or elected, and (B) automatically grant to
     each individual who is re-elected to serve as a non-employee Board member
     an option to purchase 2,000 shares of Common Stock for each full year of
     the term for which the non-employee Board member is re-elected to the
     Board. The 1997 Amendment and the 1998 Amendment were approved by the
     stockholders of the Corporation at the 1998 Annual Meeting.

          In addition, on March 6, 2001, the Board unanimously adopted an
     amendment to the Plan (the "2001 Amendment") to (i) increase the maximum
     number of shares of Common Stock available for issuance over the term of
     the Plan by an additional 1,500,000 shares effective January 1, 2002, (ii)
     increase the maximum number of shares of Common Stock available for
     issuance over the term of the Plan by an additional 1,500,000 shares
     effective January 1, 2003 and (iii) under the Automatic Option Grant
     Program, effective with the 2001 Annual Meeting (A) automatically grant to
     each individual who is first appointed or elected as a non-employee Board
     member an option to purchase 7,500 shares of Common Stock (B) during any
     partial year and for each full year of the term for which the non-employee
     Board member is first appointed or elected, automatically grant an option
     to purchase 7,500 shares of Common Stock, and (C) during each full year of
     the term for which the non-employee Board member is re-elected to the
     Board, automatically grant to each individual who is re-elected to serve as
     a non-employee Board member an option to purchase 7,500 shares of Common
     Stock. The 2001 Amendment was approved by the stockholders of the
     Corporation at the 2001 Annual Meeting.

          In addition, effective February 27, 2002, the Board unanimously
     adopted an amendment to the Plan (the "2002 Amendment"), subject to
     approval by the stockholders of the Corporation to (i) increase the number
     of shares of Common Stock authorized for issuance under the Plan by an
     additional 1,962,329 shares and (ii) increase the number of shares of
     Common Stock available for issuance under the Plan effective January 1 of
     each year beginning January 1, 2003 so that the number of authorized shares
     available for new grants under the plan on each January 1 will equal the
     lesser of 4.5% of the total number of shares of Triangle Common Stock
     outstanding on the preceding December 31st or 5,000,000 shares. The 2002
     Amendment was approved by the stockholders of the Corporation at the 2002
     Annual Meeting"

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IV.  This Amendment does not supersede the terms and conditions of the Plan,
except to the extent expressly described herein.

     IN WITNESS WHEREOF, the Corporation has caused this Amendment to be
executed by its duly authorized officer, all as of the day and year first above
written.


                                                TRIANGLE PHARMACEUTICALS, INC.


                                                By:/s/ R. Andrew Finkle
                                                   --------------------
                                                R. Andrew Finkle
                                                Executive Vice President,
                                                General Counsel and Secretary

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