Background: Patients with skin of color (SOC) and Fitzpatrick skin types (FST) IV–VI frequently develop acne. Objective: Evaluate subject-reported outcomes after treatment with adapalene 0.3%/ benzoyl peroxide 2.5% gel (0.3% A/BPO) in subjects with SOC and moderate to severe acne vulgaris. Methods: This was an open-label interventional study conducted in 3 countries (Mauritius, Singapore, and USA) in subjects of Asian, Latin-American, or black/African-American ethnicity, with an Investigator’s Global Assessment (IGA) of moderate or severe facial acne (enrollment 2:1), and FST IV to VI. For 16 weeks, subjects applied 0.3% A/BPO (once daily) and utilized a skin care regimen (oil control foam wash and oil control moisturizer SPF30). Assessments included quality of life (QoL) and subject questionnaires, IGA, Investigator’s Global Assessment of Improvement (GAI), postinflammatory hyperpigmentation (PIH; if present at baseline), and safety. Results: Fifty subjects were enrolled: 20 Asians, 17 black/African-Americans, and 13 Latin-Americans. Most had FST IV (74%) or V (22%), with moderate (70%; IGA 3) or severe (30%; IGA 4) acne. At week 16, 77% of subjects were satisfied or very satisfied with treatment, 56% of subjects had an IGA of 0 or 1 (clear/almost clear), and 87% had a good to excellent improvement in GAI. QoL improved throughout the study for all subjects; subject selection of “no effect at all” of acne on QoL increased from 16% of subjects at baseline to 55% at week 16. Of those with baseline PIH (60%), all were rated very mild to moderate. By week 16, the majority (75%) had no or very mild PIH, and the mean decrease in PIH was 27%. There were no adverse events leading to study discontinuation. Conclusion: Patients with SOC and moderate or severe facial acne reported high satisfaction with 0.3% A/BPO treatment and experienced good tolerability, improved QoL, treatment efficacy, and improvement in PIH. Clinicaltrials.gov number: NCT02932267 J Drugs Dermatol. 2019;18(6):514-520.