The goal of this study was to identify sociodemographic, psychopathological, and obstetric risk factors associated with postnatal depression (PND) and their relative weight. A cross-sectional two-stage design was used. All consecutive women receiving a routine check-up 6 weeks postpartum at Obstetric Services during a 1-year period were included. In the first stage, women completed the Edinburgh Post-natal Depression Scale (EPDS). In the second stage, mothers with EPDS scores > or =9 and a randomized sample of 16% with EPDS <9 were explored through a structured clinical interview to diagnose DSM-IV PND (major and minor depression). Variables were entered into stepwise regression models. A total of 1,201 women were recruited and did the EPDS; 261 women with EPDS scores > or =9 and 151 with EPDS scores <9 were selected. Three hundred and thirty-four women agreed to be interviewed and 100 were diagnosed with PND. Family caregiver role (defined as women who have to take care of handicapped or ill relatives) was associated with a 4.4-fold increase in risk for major PND (OR: 4.39, 95%CI: 1.10-17.38). Premenstrual syndrome was identified as an independent risk factor for major and minor PND (OR: 1.81, 95%CI: 1.03-3.18). Moreover, previous depression, poor partner relationship, and lower social support were also confirmed as risk factors for PND. Both family caregiver role and premenstrual syndrome should be considered for inclusion in the rating scales of pregnant women at risk for PND.