Relevance. Acne is one of the most common dermatoses affecting the face. Among young people, the proportion of patients with acne is 65–85%. Despite the large repertoire of medicines and treatments, the search for new molecules and treatments of acne is still underway. The use of drug combinations in treatment of acne is of great interest all over the world with a view to achieve consistent results and improve patients’ adherence to therapy. The use of combination therapy with agents having complementary mechanisms of action is of particular importance. Drug Combinations affect larger number of pathogenic factors of acne development (excessive follicular hyperkeratosis, reproduction of Propionibacterium acnes, inflammation). Objective. The objective of the study is to compare the efficacy and safety of 15% azelaic acid gel, 0.1% adapalene gel, and 1% clindamycin gel in combination treatment of patients with mild to moderate papulopustular acne. Material and methods. We conducted 6-week-long open comparative study, which involved 100 patients with mild to moderate papulopustular acne. All patients underwent clinical examination (clinical and biochemical blood and urine tests). The effectiveness of the therapy was evaluated based on dermatological status and Dermatological Quality of Life Index (DQOLI) before and after therapy. Results and conclusions. Combination therapy using preparations of 15% azelaic acid gel and 0.1% adapalene gel was effective for clinical improvement and recovery in 68% of the observations. Combination of preparations of 15% azelaic acid gel and 1% clindamycin gel resulted in similar effect in 76% of patients. Administration of combination of topical agents can improve therapeutic efficacy and decrease the incidence of side effects of topical therapy.