Postpartum depression is a common psychiatric disorder in parturients after delivery. The etiology remains unclear, and multiple factors may be involved. In this study, we investigated whether epidural labor analgesia was associated with a decreased risk of postpartum depression development. Two hundred fourteen parturients who were preparing for a vaginal delivery were enrolled in this prospective cohort study. Epidural labor analgesia was performed in 107 of 214 patients on their request. Parturients' mental status was assessed with the Edinburgh Postnatal Depression Scale at 3 days and 6 weeks after delivery. A score of 10 or higher on the scale at 6 weeks was used as an indication of postpartum depression. Parturients' characteristics together with perinatal variables were collected. Multivariate logistic regression analysis was performed to assess an association between the use of epidural analgesia and the occurrence of postpartum depression. Postpartum depression occurred in 14.0% (15 of 107) of parturients who received epidural labor analgesia and in 34.6% (37 of 107) of those who did not (P < 0.001). Use of epidural labor analgesia was associated with a decreased risk of postpartum depression (odds ratio OR 0.31, 95% confidence interval CI, 0.12-0.82, P = 0.018). Attendance at childbirth classes during pregnancy (OR 0.30, 95% CI, 0.12-0.79, P = 0.015) and continued breast-feeding after delivery (OR 0.02, 95% CI, 0.00-0.07, P < 0.001) were also associated with decreased risks of postpartum depression. A high Edinburgh Postnatal Depression Scale score at 3 days postpartum was associated with an increased risk of postpartum depression (OR 1.20, 95% CI, 1.05-1.37, P = 0.009). Epidural labor analgesia was associated with a decreased risk of postpartum depression. Further study with a large sample size is needed to evaluate the impact of epidural analgesia on the occurrence of postpartum depression.