This study aimed to investigate the effect of epidural analgesia on the incidence of postpartum depression. A prospective study was conducted including 229 primiparous women who delivered vaginally at term with a single fetus. Participants were randomized into two groups: a control group (116 cases) and a study group (113 cases) based on whether they chose to receive epidural analgesia. The incidence of postpartum depression in the study group was lower than that in the control group (14.2% vs. 29.3%), and the difference was statistically significant (P=0.006). There were no significant differences between the two groups in terms of breastfeeding rate or EPDS scores at 42 days postpartum (P > 0.05). Single-factor analysis of postpartum depression showed that 19 factors, including gestational weeks, fetal suction, HB, internal medicine diseases, income less than 10,000 yuan, dissatisfaction with housing, history of surgery, labor analgesia, not attending antenatal classes, premenstrual syndrome, pre-delivery SDS score, neonatal asphyxia, EMS score at 3 days postpartum, EPDS score at 3 days postpartum, breastfeeding rate at 3 days postpartum, neonatal hospitalization, comfort satisfaction, EPDS score at 42 days postpartum, and breastfeeding rate at 42 days postpartum, were significantly associated with the occurrence of postpartum depression between the two groups (P < 0.05). Multivariate logistic regression analysis of postpartum depression showed that epidural analgesia was an independent protective factor, while neonatal hospitalization after birth and general comfort satisfaction were two risk factors. The use of epidural analgesia during labor can effectively improve the quality of obstetrics and reduce the risk of postpartum depression, and is worthy of promotion and application.