Background. Although several studies have reported that repetitive transcranial magnetic stimulation (rTMS) treatment has demonstrable efficacy in patients with depression, the parameters needed to optimize therapeutic efficacy remain unclear. To this end we determined the efficacy of low-frequency right rTMS to the dorsolateral prefrontal cortex (DLPFC) compared to two forms of bilateral rTMS to the DLPFC: (1) sequential low-frequency right-sided followed by high-frequency left-sided rTMS and (2) sequential low-frequency rTMS to both hemispheres. Method. A total of 219 patients with treatment-resistant depression (TRD) were randomized to a 4-week course of rTMS applied with one of the three treatment conditions. Outcomes were assessed with standard rating scales. Results. Overall, slightly more than 50 of the patients achieved clinical response criteria. There was no substantial difference in response between the unilateral and bilateral treatment groups. Successful response to rTMS was predicted by a greater degree of baseline depression severity. Conclusions. There is no substantial difference in efficacy between unilateral right-sided rTMS and the two forms of bilateral rTMS assessed in the study. Furthermore, our results call into question the specificity between frequency and laterality and rTMS response.