Major depression is common among women. The highest rates of depressive episodes occur during the reproductive and menopausal transition years. Obstetrician-gynecologists (ob-gyns) recognize the need for depression management as part of routine care but have inadequate training and lack the resources to diagnose and treat depression. Because more than one third of nonpregnant patients use ob-gyns as their sole or primary provider of routine care, there is a clear need for ob-gyns to play an increased role in the diagnosis and treatment of depression. Collaborative depression care intervention models have been effective in primary care practice settings but have not been adapted for use in obstetrics and gynecology settings. The aim of this randomized controlled trial was to evaluate a collaborative care intervention program for depression treatment in obstetrics and gynecology clinics. The study was conducted at 2 urban academic obstetrics and gynecology clinics. Participants were screen-positive women (Patient Health Questionnaire 9 score of at least 10) who met the criteria for major depression, dysthymia, or both after a structured psychiatric interview (Mini-International Neuropsychiatric Interview). A total of 205 women were randomized to 12 months of collaborative depression management (n = 102) or usual care (n = 103). Outcomes were compared at 6, 12, and 18 months. The change from baseline to 12 months in depression symptoms and functional status was the primary study outcomes. Secondary outcomes included at least a 50% decrease in depressive symptoms, complete remission of symptoms, global improvement, treatment satisfaction, and quality of care. On average, participants were 39 years old; 44% were nonwhite, and 56% had posttraumatic stress disorder. There was greater improvement in depressive symptoms among women in the intervention group than in the usual care group both at 12 months (P < 0.001) and 18 months (P < 0.004). Compared with the usual care group, the intervention group had improved functioning at 18 months (P < 0.05) and were more likely to have at least a 50% decrease in depressive symptoms at 12 months; the relative risk (RR) was 1.74, with a 95% confidence interval (CI) of 1.11 to 2.73 (P = 0.015). Women in the intervention group were more likely to have at least 4 specialty mental health visits at 6 months (RR, 2.70; 95% CI, 1.73–4.20; P < 0.001) and 12 months (RR, 2.53; 95% CI, 1.63–3.94; P < 0.001); and had higher rates of using an adequate dose of antidepressant at 6 months (RR, 1.64; 95% CI, 1.03–2.60; P = 0.04) and 12 months (RR, 1.71; 95% CI, 1.08–2.73; P = 0.02). Intervention also was associated with greater satisfaction with care at 6 months (RR, 1.70; 95% CI, 1.19–2.44; P < 0.004) and 12 months (RR, 2.26; 95% CI, 1.52–3.36; P < 0.001). These data show that the integrated collaborative depression care program improves depressive and functional outcomes as well as patient satisfaction with care in an obstetrics-gynecology setting. The program is feasible and can be adapted in this setting.