Background: Topical retinoid based combinations are recommended to enhance the outcome of acne treatment. Adapalene-benzoyl peroxide (BPO) combination gel was approved in 2009 for acne treatment. The aim of this study was to evaluate the efficacy and tolerability of adapalene 0.1%-benzoyl peroxide 2.5% combination gel compared to adapalene 0.1% gel monotherapy and benzoyl peroxide 2.5% gel monotherapy in treatment of acne vulgaris in Indian patients.Methods: A randomized, parallel group, investigator-blind clinical trial was conducted from September 2014 to September 2015 in the Dermatology outpatient department. The patients were randomized into three groups of adapalene 0.1% gel, benzoyl peroxide 2.5% gel, and adapalene 0.1%-benzoyl peroxide 2.5% combination gel. The patients were asked to apply the allocated gel to the face in the evening for 12 weeks. Efficacy was evaluated using percent of reduction in total, inflammatory, and non-inflammatory lesions and success rate while tolerability was assessed by evaluating skin dryness, erythema, stinging or burning sensation and scaling at baseline and 1, 2, 4, 8, and 12 weeks.Results: At the end of 12 weeks, the success rate reached 37.2% with adapalene-BPO combination gel compared to 23.3% and 19.4% for adapalene and benzoyl peroxide gel monotherapy respectively. Adapalene-BPO combination gel was significantly effective in the reduction of total, non-inflammatory and inflammatory lesions by 75.9%, 75.4%, and 74.7% respectively compared to the corresponding monotherapies. Side effects with adapalene–BPO combination gel were mild and transient.Conclusion: Adapalene–BPO combination gel was more efficacious and better tolerated than adapalene and benzoyl peroxide gel monotherapy.