Background: Acne vulgaris, a common skin disorder is treated by multitargeted approach. There is scarce data evaluating adapalene in combination with other drugs. Objectives: We compared the efficacy and safety of efficacy of topical combination of 1% Clindamycin and 0.1% Adapalene with 2.5% Benzoyl peroxide and 0.1% Adapalene in mild to moderate acne. Methods: 80 patients, attending outpatient department of dermatology with mild to moderate acne vulgaris as per Indian Acne Alliance grading were randomised into two groups with 40 patients in each group. Group A received topical 1% Clindamycin and 0.1% Adapalene and group B received 2.5% Benzoyl peroxide and 0.1% Adapalene. The efficacy of the drugs was evaluated at 4, 8 and at 12 weeks follow up by spot counting of acne lesions on face. The number of inflammatory lesions (pustules, papules) and non inflammatory lesions (open and closed comedones) were noted and compared between the two groups. Results: The mean number of lesions namely comedones, papules, pustules and nodules were counted for each group during each visit and compared between the groups. There was no statistically significant difference in the reduction of lesions between both the groups (p > 0.001). There was slightly higher irritation with the adapalene benzoyl peroxide group but was statistically insignificant. Conclusion: Hence both the combinations can be safely prescribed to the patients.