BackgroundPostpartum depression is a major psychiatric disorder associated with maternal suicide and child developmental disturbances. In this study, we aimed to investigate whether general anesthesia for cesarean delivery is associated with a higher rate of new-onset depression after delivery than neuraxial anesthesia. MethodsThis is a nationwide retrospective cohort study using data retrieved from the National Health Insurance Research Database between 2014 and 2018. Women who had cesarean delivery under general or neuraxial anesthesia were enrolled. After 1:4 propensity score matching, there were 4544 and 18,176 women under the general and neuraxial anesthesia groups, respectively. The primary outcome was new-onset depression diagnosed after delivery in a time-to-event analysis setting. ResultsAfter propensity-score matching, the rate of new-onset depression diagnosed within 1 year was 1.10 % (50/4488) and 0.86 % (157/18176) after cesarean delivery under general and neuraxial anesthesia, respectively. For depression diagnosed within 90 days of delivery, significant difference between the two groups was noted (0.51 % vs. 0.30 %, P = 0.031). In the time-to-event analysis with Cox regression model, women who delivered under general anesthesia were associated with significantly higher risk of postpartum depression within 90 days (Hazard ratio [HR], 1.71; 95 % CI, 1.05–2.79) compared with those under neuraxial anesthesia. LimitationsThe observational design only allows asserting association, rather than establishing causality between exposure and outcomes. ConclusionsWomen who underwent cesarean delivery under general anesthesia had a higher risk of subsequent depression within 90 days than those under neuraxial anesthesia. Early screening for depressive disorders might facilitate timely management.