Acne is the most common skin disease of teenagers and affects up to 80—90% of young people. Acne is not a life-threatening disease, but localization of the process on the visible areas of the skin can significantly affect the social and psychological adaptation of a person. Despite significant progress in the therapy of acne, improvement of treatment is still an urgent issue. Even in the case of mild forms of the disease, the most effective combined methods should be preferred at the very beginning of treatment, if the disease is accompanied by severe social maladjustment. Objective. The objective of the study is to compare the efficacy and safety of Azelik (15% azelaic acid gel), Klindovit (1% clindamycin gel), and Klenzit (0.1% adapalene gel) in the treatment of mild to moderate acne. Material and methods. Open comparative 6 weeks-long study involved 386 patients with mild to moderate papulopustular acne dominated by pustules. Dermatological status was described and dermatological life quality index (DLQI) was assessed before and after treatment in order to evaluate the effectiveness of therapy. Results and Conclusions. Clinical results demonstrated high therapeutic efficacy of complex treatment regimens: Klindovit + Azelik in the treatment of mild to moderate papulopustular acne dominated by pustules; Azelik + Klenzit in the treatment of mild to moderate papulopustular acne dominated by papules. These regimens may be recommended for practical use in ambulatory network. No adverse events were observed during long-term administration of these external therapeutic complexes; the results of patients’ subjective evaluation clearly demonstrated the high level of safety and tolerability. Combination therapy resulted in significant improvement of patients’ DLQI.