OBJECTIVE: This study investigated whether a preventive intervention based on the principles of interpersonal psychotherapy administered to pregnant women would reduce the risk of postpartum major depression. METHOD: Thirty-seven pregnant women receiving public assistance who had at least one risk factor for postpartum depression were randomly assigned to a four-session group intervention or to a treatment-as-usual condition. Thirty-five of the women completed the study. Structured diagnostic interviews were administered to assess for postpartum major depression. RESULTS: Within 3 months after they gave birth, six (33%) of the 18 women in the treatment-as-usual condition had developed postpartum major depression, compared with none of the 17 women in the intervention condition. CONCLUSIONS: A four-session interpersonal-therapy-oriented group intervention was successful in preventing the occurrence of major depression during a postpartum period of 3 months in a group of financially disadvantaged women.