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. 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 & Muñoz, 1998). Outcomes were assessed at baseline and at 1 week and 3 months postintervention. Repeated measures analysis of variance indicated that there was a significant Time× Condition interaction, F (2, 112)= 4.1, p=. 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, χ 2 (1, N= 59)= 5.18, p<. 05. 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.