Background: A limited number of studies have investigated the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of resistant depression in an outpatient private practice setting. We hypothesized that rTMS would be safe and effective in the treatment of resistant depression in a nonresearch population. Methods: We treated 22 outpatients with unipolar or bipolar depression who were experiencing a moderate to severe treatment-resistant major depressive episode (MDE). Treatment was based on a flexible dose schedule of either 5Hz or 10 Hz rTMS applied over the left dorsolateral prefrontal cortex with modified parameters. Assessments were performed at baseline, then on a weekly basis. The patients had received at least 2 trials of antidepressant medication of an adequate dose and duration without satisfactory improvement in the index MDE. Results: There was a significant change in Montgomery-Asberg Depression Rating Scale scores from baseline (29.14+/-5.85) to the end of week 4 (16.27+/-11.20); 50.00% (11/22) were responders and 40.9% (9/22) achieved remission. No major side effects were observed aside from mild headache in some patients. Conclusions: rTMS applied to the left dorsolateral prefrontal cortex was safe and effective in an important subset of outpatients with a moderate to severe MDE in a naturalistic setting. Outcomes demonstrated response rates similar to research populations. Further larger studies are needed to confirm the safety and effectiveness of rTMS in naturalistic conditions.