Background: The correct therapeutic management of acne should include a maintenance therapy with topical retinoids to prevent recurrences after discontinuing a successful treatment. Objective: To investigate the efficacy of a 12-month maintenance treatment with adapalene 0.1% and benzoyl peroxide (BPO) 2.5% fixed combination gel to control acne relapse after treatment with oral isotretinoin (OI). Methods: The study consisted of 2 phases, namely an active treatment phase (AP) and a maintenance phase (MP). In the AP, 70 consecutive patients with moderate to severe acne were treated with OI until acne remission. Then, patients entered the MP and were treated with adapalene-BPO fixed combination once daily for 12 months. The primary efficacy parameter was the relapse rate during MP. Results: Sixty-eight patients completed the study. Relapse occurred in 2 patients (2.94%). Conclusions: Comparing our findings with published data, the association of a topical retinoid and BPO seems to provide favorable evidence for this combination as maintenance therapy.