This prospective cohort study compares the breastfeeding outcomes of women exposed to selective serotonin reuptake inhibitor (SSRI) antidepressants at the time of delivery, those who discontinued use prior to delivery, and those not exposed. Participants include 466 pregnant women who enrolled in the California Teratogen Information Service Clinical Research Program (CTIS) over 10 years. In bivariate analyses, breastfeeding rates were significantly different across SSRI exposure groups, with unexposed women having the highest rates. We used logistic regression to examine the relationship between SSRI exposure and breastfeeding outcomes. After adjustment for potential confounders, those exposed to an SSRI both prior to delivery (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.20-0.94) and at the time of delivery (OR, 0.34; 95% CI, 0.16-0.72) were significantly less likely to initiate breastfeeding as compared to unexposed women. Women exposed to an SSRI during pregnancy appear to be at risk for poorer breastfeeding outcomes and may benefit from additional education and support.