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To determine whether a Nurse-Community Health Worker (CHW) home visiting team, in the context of a Medicaid enhanced prenatal/postnatal services (EPS), would demonstrate greater reduction of depressive symptoms and stress and improvement of psychosocial resources (mastery, self-esteem, social support) when compared with usual Community Care (CC) that includes Medicaid EPS delivered by professionals. Greatest program benefits were expected for women who reported low psychosocial resources, high stress, or both at the time of enrollment. Medicaid eligible pregnant women (N = 613) were randomly assigned to either usual CC or the Nurse-CHW team. Mixed effects regression was used to analyze up to five prenatal and postnatal psychosocial assessments. Compared to usual CC, assignment to the Nurse-CHW team resulted in significantly fewer depressive symptoms, and as hypothesized, reductions in depressive symptoms were most pronounced for women with low psychosocial resources, high stress, or both high stress and low resources. Outcomes for mastery and stress approached statistical significance, with the women in the Nurse-CHW group reporting less stress and greater mastery. Women in the Nurse-CHW group with low psychosocial resources reported significantly less perceived stress than women in usual CC. No differences between the groups were found for self-esteem and social support. A Nurse-CHW team approach to EPS demonstrated advantage for alleviating depressive symptoms in Medicaid eligible women compared to CC, especially for women at higher risk.