Background: Age and gender have become increasingly important considerations in acne therapy. Adapalene plus benzoyl peroxide (A/BPO) is a first-line recommended acne therapy. In 2015, the FDA approved a higher concentration A/BPO for the treatment of acne vulgaris, A/BPO gel 0.3%/2.5%. We sought to investigate the influence of gender and age on the efficacy and safety of topical A/BPO 0.3%/2.5%. Methods: This was a post hoc subanalysis of a multicenter, randomized, double-blind, parallel group, 12-week, vehicle- and active-controlled study of A/BPO gel 0.3%/2.5% and vehicle gel treatment in men and women ≥12 years old with moderate to severe acne vulgaris (Investigator global assessment [IGA] of 3 or 4). Efficacy measurements included success rate, change in inflammatory/noninflammatory lesions from baseline to week 12, safety, and tolerability. The intent to treat (ITT) and safety populations were analyzed. Demographics and disposition were analyzed using descriptive statistics, categorical variables by frequency and percentage, and continuous variables by means and the standard error of the means. Results: The A/BPO gel 0.3%/2.5% treatment group included 217 subjects. By age: 111 were ≤ 17 years old, and 106 were ≥ 18 years old. By gender: 104 were men, and 113 were women. Regardless of age or gender, A/BPO 0.3%/2.5% was safe, tolerable, and significantly superior to vehicle in success, inflammatory lesion reduction, and noninflammatory lesion reduction (P ≤ .05). Summary: A/BPO 0.3%/2.5% reduced lesion counts and was a safe and effective acne therapy regardless of age or gender. These results support the use of A/BPO 0.3%/2.5% as a first line acne therapy in all subjects 12 and older