Objective To estimate the efficacy of acupuncture for depression during pregnancy in a randomized controlled trial. Methods A total of 150 pregnant women who met Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for major depressive disorder were randomized to receive either acupuncture specific for depression or one of two active controls: control acupuncture or massage. Treatments lasted 8 weeks (12 sessions). Junior acupuncturists, who were not told about treatment assignment, needled participants at points prescribed by senior acupuncturists. All treatments were standardized. The primary outcome was the Hamilton Rating Scale for Depression, administered by masked raters at baseline and after 4 and 8 weeks of treatment. Continuous data were analyzed using mixed effects models and by intent to treat. Results Fifty-two women were randomized to acupuncture specific for depression, 49 to control acupuncture, and 49 to massage. Women who received acupuncture specific for depression experienced a greater rate of decrease in symptom severity (P < .05) compared with the combined controls (Cohen's d = 0.39, 95% confidence interval [CI] 0.01–0.77) or control acupuncture alone (P < .05; Cohen's d = 0.46, 95% CI 0.01–0.92). They also had significantly greater response rate (63.0%) than the combined controls (44.3%; P < .05; number needed to treat, 5.3; 95% CI 2.8–75.0) and control acupuncture alone (37.5%; P < .05: number needed to treat, 3.9; 95% CI 2.2–19.8). Symptom reduction and response rates did not differ significantly between controls (control acupuncture, 37.5%; massage, 50.0%). Conclusion The short acupuncture protocol demonstrated symptom reduction and a response rate comparable to those observed in standard depression treatments of similar length and could be a viable treatment option for depression during pregnancy. CLINICAL TRIAL REGISTRATION: Clinicaltrials. gov, www.clinicaltrials.gov, NCT00186654.