Background: Deep brain stimulation is increasingly being used for treatment-resistant depression. Blinded, randomized controlled trials of active versus sham treatment have been limited to small numbers. Method: We performed a systematic review and meta-analysis on the effectiveness of deep brain stimulation (DBS) in depression. Cochrane Central Register of Controlled Trials, PubMed/Medline, Embase and PsycINFO, Chinese Biomedical Literature Service System, and China Knowledge Resource Integrated Database were searched for single- or double placebocontrolled, crossover, and parallel-group trials in which DBS was compared with sham treatment using validated scales. Results: Ten papers from nine studies met inclusion criteria, all but two of which were doubleblinded RCTs. The main outcome was a reduction in depressive symptoms. It was possible to combine data for 190 participants. Patients on active, as opposed to sham, treatment had a significantly higher response (OR = 5.50; 95% CI = 2.79, 10.85; p < .0001) and reductions in mean depression score (SMD = –0.42; 95% CI = –0.72, -0.12; p = .006). However, the effect was attenuated on some of the subgroup and sensitivity analyses, and there were no differences for most other outcomes. In addition, 84 participants experienced a total of 131 serious adverse effects, although not all could be directly associated with the device or surgery. Finally, publication bias was possible. Conclusions: DBS may show promise for treatment-resistant depression but remains an experimental treatment until further data are available.