Inclusion Criteria:  Male or female patients will be considered eligible for participation in the study if all of the following inclusion criteria are satisfied prior to randomization:  Has completed and signed an appropriately administered Informed Consent Form (ICF) prior to any study-related procedures. Patients less than 18 years of age (or as required by state law) must sign an Assent Form for the study and a parent or legal guardian must sign the ICF. Is 12 years of age or older. Has facial acne vulgaris with an IGA score of moderate (3) or severe (4). Is willing and able (with assistance from a caregiver as necessary) to both apply AMZEEQ® and take oral isotretinoin capsule(s) as directed, comply with study instructions, and commit to all follow-up visits for the duration of the study. If female of child-bearing potential (FOCBP), must have two negative pregnancy tests, one being serologic, within the screening period. Is willing to commit to true abstinence from heterosexual contact (which must be reviewed at each study visit and source documented) or agreed to use, and be able to comply with, effective contraception without interruption, prior to starting treatment as detailed below, during study period. For FOCBP who may participate in the study, the following methods of contraception, if properly used, are generally considered reliable with the following wait periods prior to having relations: oral contraceptives; vaginal contraceptive ring and patch contraceptives (one full cycle; e.g., 4 to 8 weeks); injection contraceptives (more than 7 days); intrauterine device or implantable hormone contraceptives (more than 7 days); surgical sterilization (bilateral tubal ligation) or a vasectomized partner (each, more than 6 months); male condom with intravaginal spermicide or diaphragm/cervical cap with spermicide (effective with proper use without a waiting period). If sexually active male patient, must practice true abstinence (which must be reviewed at each study visit) or agree to use a condom with intravaginal spermicide during sexual contact with a pregnant female or a FOCBP, while participating in the study, during dose interruptions, and for at least 30 days following treatment discontinuation, unless patient has undergone a successful vasectomy. Male patients should refrain from making sperm donations at any time during study participation and for at least 30 days following treatment discontinuation. Is willing to minimize exposure of the treated skin to ultraviolet light (e.g. avoid excessive sunlight, agree to not use tanning beds) and extremes in weather, such as wind or cold, throughout the study. In the investigator's opinion, patient is in good general health and is free of any disease state or physical condition that exposes the patient to an unacceptable risk by study participation or impairs the evaluation of the patient or the treatments by participating in the study.  Exclusion Criteria:  Patients who meet any of the following will be excluded from the study:  Female who is pregnant, lactating or breastfeeding, or is planning a pregnancy during the study. Acne conglobata, acne fulminans, secondary acne (chloracne, drug-induced acne), or any dermatological condition of the face (such as seborrhea, atopic dermatitis or basal cell carcinoma) that would require the use of confounding therapies or facial hair (eg, beard, sideburns, mustache) that could either interfere with clinical evaluations. Sunburn on the face. Severe systemic disease that might interfere with the conduct of the study or the interpretation of the results. Abnormal Screening laboratory values that are considered clinically significant. Patient is currently enrolled in another investigational drug or device study or is using or has used an investigational drug or investigational device treatment within 30 days of randomization. Patient, who in the opinion of the investigator, is unable or unlikely to comply with the requirements of the study protocol.  Patients who have a history of any of the following will be excluded:  Allergy to tetracycline-class antibiotics or to any ingredient in the study drug Pseudomembranous colitis or antibiotic-associated colitis Hepatitis or liver damage or renal impairment Known or suspected premalignant or malignant disease (excluding successfully treated skin cancers)  Patients who have used the following medications (topical refers only to the facial area) will not be eligible:  Within 1 week prior to randomization:  Medicated facial cleansers Topical acne treatments (other than those listed below)  Within 4 weeks prior to randomization:  Topical retinoids on the face Topical anti-inflammatories eg, PDE-4 inhibitors, calcineurin inhibitors and corticosteroids on the face Topical corticosteroids on body areas other than the face for more than 15 consecutive days and on more than 10% of body surface area. In flexural body areas, such as axillary and inguinal regions, only mild topical corticosteroids and allowed for short term use (≤15 consecutive days). Systemic antibiotics Systemic acne treatments  Within 12 weeks prior to randomization:  Systemic retinoids Systemic corticosteroids (Note: Intranasal and inhaled corticosteroids may be used throughout the study). The following medications have been used less than the specified length of stable usage and patients must not initiate or change the dosing regimen during the course of the study: 3 months: hormonal contraceptives and therapies which also include testosterone replacement or supplementation. Patient has any acute illness (eg, infection) within 48 hours of randomization, which, in the investigator's opinion, is considered significant. Patient has a history of sensitivity to any of the ingredients in the medications.  Documented history of depression or self-harm that is not, in the opinion of the Investigator, currently adequately controlled with medication or in remission. Or, the presence of significant uncontrolled neuropsychiatric disorder, are clinically judged by the investigator to be at risk for suicide, or have a "yes" answer to any of the following at Screening or Baseline:  Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) on the "Suicidal Ideation" portion of the Columbia Suicide Severity Rating Scale (C-SSRS) or Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the C-SSRS or Any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act or behavior) on the "Suicidal Behavior"portion of the C-SSRS.  Note: A patient does not necessarily have to be excluded if they have self-injurious behavior that would be classified as non-suicidal self-injurious behavior. If this situation arises, the subject should be referred to a psychiatrist or appropriately trained professional as indicated.  Drug addiction or alcohol abuse (within the last 2 years). Patient has history of previous use of isotretinoin.