OBJECTIVE: Infertility is associated with many established risk factors (RF) for postpartum depression (PPD) but little is known about the development of PPD in infertility patients after delivery. This study investigates whether women with history of primary infertility are more likely to experience PPD. DESIGN: Prospective cohort MATERIALS AND METHODS: We screened primiparas women immediately postpartum and determined whether it took a year or more to conceive. Block enrollment of patients with and without infertility was performed. Participants responded to questions assessing multiple RF for PPD. At the 6-week postpartum visit, participants completed the Edinburgh Postpartum Depression Scale. Bivariate associations of PPD with different variables were tested using Student's t-test and chi-square test. Multivariable logistic regression analysis was performed to assess the relationship between infertility and PPD. RESULTS: A total of 160 subjects were enrolled. Six were lost to follow-up leaving 154 for analysis, 81 with history of infertility and 73 controls. The mean age was 30.5±5.4 yrs, with no difference between the two groups. Of the previously infertile patients, 47% conceived spontaneously, 25% with oral ovulation induction agents, 14% with injectable agents and 15% after IVF. 17% of infertility patients and 13% of controls had positive screens for PPD (p=0.54). PPD was significantly associated with prenatal depression (p<0.01), not married or cohabiting with partner (p=0.01), financial problems (p=0.02) and inadequate emotional support (p=0.03). Results of logistic regression did not show an independent association between infertility and either PPD (p=0.42) or prenatal depression (p=1.0), which was the only significant predictor of PPD (p<0.01;OR 4.7;95% CI=1.7-12.5). CONCLUSIONS: Women at risk for PPD should be identified during pregnancy and screened postpartum for early detection of PPD. Our data is reassuring for health professionals and patients that history of infertility is not an independent RF for PPD.