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Introduction: Epidural analgesia has become a universal intervention for relieving labor pain, and its effect on the pelvic floor is controversial. Aim: To investigate the effect of epidural analgesia on pelvic floor dysfunction (PFD) in primiparous women at 6 months postpartum. Methods: We performed a prospective cohort study involving 150 primiparous women in preparation for vaginal delivery, with 74 (49.3%) receiving epidural analgesia. Baseline demographic and intrapartum data were collected. At 6 months postpartum, PFD symptoms, including stress urinary incontinence, overactive bladder, defecation disorder, pelvic organ prolapse, and 4 kinds of sexual dysfunction (arousal disorder, low sexual desire, dyspareunia, and orgasm disorder), were evaluated. Pelvic floor muscle (PFM) function and postpartum depression were also assessed. Multivariate logistic regression was applied to identify factors associated with the PFD symptoms affected by epidural analgesia. Main outcome measure: PFD symptoms and sexual dysfunction were evaluated through Pelvic Floor Distress Inventory-20 (PFDI-20) and Female Sexual Function Index (FSFI-12). PFM function was examined with palpation and surface electromyography (sEMG). Postpartum depression was assessed using Self-Rating Depression Scale (SDS). Results: At 6 months postpartum, women who delivered with epidural analgesia had a higher incidence of dyspareunia (43.2% vs 26.3%, P 0.05). Multivariate logistic regression revealed that epidural analgesia (OR = 3.056, 95% CI = 1.217-7.671) and SDS scores (OR = 1.066, 95% CI = 1.009-1.127) were independent risk factors for dyspareunia. Conclusion: At 6 months postpartum in primiparous women, epidural analgesia was associated with an increased risk of postpartum dyspareunia and longer labor durations, which deserves attention for rehabilitation after delivery. Future studies with a larger sample size are needed to evaluate the impact of epidural analgesia on other PFD symptoms. Du J, Ye J, Fei H, et al. Effect of Epidural Analgesia on Pelvic Floor Dysfunction at 6 Months Postpartum in Primiparous Women: A Prospective Cohort Study. Sex Med 2021;9:100417.