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Both antenatal and postpartum depression have adverse, lasting effects on maternal and child well-being. Socioeconomically disadvantaged women are at increased risk for perinatal depression and have experienced difficulty accessing evidence-based depression care. The authors evaluated whether “MOMCare,”a culturally relevant, collaborative care intervention, providing a choice of brief interpersonal psychotherapy and/or antidepressants, is associated with improved quality of care and depressive outcomes compared to intensive public health Maternity Support Services (MSS-Plus).A randomized multisite controlled trial with blinded outcome assessment was conducted in the Seattle-King County Public Health System. From January 2010 to July 2012, pregnant women were recruited who met criteria for probable major depression and/or dysthymia, English-speaking, had telephone access, and ≥18 years old. The primary outcome was depression severity at 3-, 6-, 12-, 18-month postbaseline assessments; secondary outcomes included functional improvement, PTSD severity, depression response and remission, and quality of depression care.All participants were on Medicaid and 27 years old on average; 58% were non-White; 71% were unmarried; and 65% had probable PTSD. From before birth to 18 months postbaseline, MOMCare (n = 83) compared to MSS-Plus participants (n = 85) attained significantly lower levels of depression severity (Wald's χ2 = 6.09, df = 1, P = .01) and PTSD severity (Wald's χ2 = 4.61, df = 1, P = .04), higher rates of depression remission (Wald's χ2 = 3.67, df = 1, P = .05), and had a greater likelihood of receiving ≥4 mental health visits (Wald's χ2 = 58.23, df = 1, P < .0001) and of adhering to antidepressants in the prior month (Wald's χ2 = 10.00, df = 1, P < .01).Compared to MSS-Plus, MOMCare showed significant improvement in quality of care, depression severity, and remission rates from before birth to 18 months postbaseline for socioeconomically disadvantaged women. Findings suggest that evidence-based perinatal depression care can be integrated into the services of a county public health system in the United States.Clinical Trial Registration: ClinicalTrials.govNCT01045655.