Objective: To assess the efficacy of a 6-week cognitive-behavioral intervention in preventing the onset of perinatal depression and reducing depressive symptoms among low-income women in home visitation programs. Method: Sixty-one women who were pregnant or who had a child less than 6 months of age and who were assessed as at risk for perinatal depression were randomized to a 6-week, group-based cognitive-behavioral intervention or usual home visiting services. Study participants were predominately African American, unmarried, and unemployed. Intervention sessions were led by a licensed clinical social worker or clinical psychologist. Home visitors provided 1-on-1 reinforcement of key intervention messages between group sessions. Depressive symptoms were measured with the Beck Depression Inventory-II (Beck, Steer, & Brown, 1996), and major depressive episodes were measured with the Maternal Mood Screener (MMS; Le & Munoz, 1998). Outcomes were assessed at baseline and at 1 week and 3 months postintervention. Results: Repeated measures analysis of variance indicated that there was a significant Time x Condition interaction, F(2, 112) = 4.1, p = 0.02. At 3 months postintervention, 9 of 27 (33%) women receiving usual care reported levels of depressive symptoms that met clinical cutoff for depression on the MMS compared with 3 of 32 (9%) women in the intervention condition, [chi][superscript 2](1, N = 59) = 5.18, p less than 0.05. Conclusion: This study provides preliminary data on the efficacy of a cognitive-behavioral intervention to prevent perinatal depression among home visiting clients and suggests it is feasible to embed such an intervention in home visitation programs. A larger trial is warranted to attempt to replicate study findings. (Contains 3 tables and 1 figure.)