OBJECTIVES To investigate the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS), venlafaxine or a combination of both treatments as a maintenance treatment in patients with treatment-resistant depression (TRD). METHODS In a three-arm open-label study, 66 patients, including 45 remitters, who responded to rTMS (n = 25), venlafaxine (n = 22), or a combination of both treatments (n = 19) continued to receive the treatment that led to a response as a maintenance treatment over 12 months. Maintenance rTMS was administered twice per week for 1 month, once per week for 2 months, and once every 2 weeks for 9 months. Venlafaxine was maintained at the dose that induced a clinical response (150 or 225 mg/day). RESULTS After the 12-month follow-up, the rates of remitters (HDRS < 8) were not different between the three groups (χ2 = 1.25; P = .3). The rates of patients who not relapsed (HDRS < 15) were not different between groups (χ2 = 0.33; P = .8): 40.0% in the rTMS group, 45.1% in the venlafaxine group and 36.9% in the combination group. CONCLUSIONS The three maintenance approaches exhibited similar efficacies in relapse prevention and the maintenance of remission in patients with TRD.