OBJECTIVE To investigate the effectiveness of 10% povidone-iodine formulation as a vaginal irrigation agent in patients undergoing hysterectomy to prevent postoperative infection. METHODS The prevalence of postoperative infection in 277 and 132 patients who underwent preoperative vaginal cleaning with 500 mL of distilled water and 20 mL of 10% povidone-iodine solution, respectively, were compared in this retrospective study. RESULTS Postoperative infection was observed in 15.6% of the overall patient population. The rate of postoperative infection was significantly higher in patients treated with 10% povidone-iodine formulation than in those treated with distilled water (21.4% vs 12.8%, P = 0.040). Besides the agents of vaginal irrigation, operation time, length of hospital stay and rate of intraoperative complications affected the prevalence of postoperative infection. The multivariate analysis ranked the use of 10% povidone-iodine formulation for vaginal irrigation as the second top factor contributing to postoperative infection (relative risk: 1.9 when compared to distilled water). CONCLUSIONS Preoperative vaginal irrigation with 10% povidone-iodine formulation led to a significantly higher rate of postoperative infection than did preoperative vaginal irrigation with distilled water. For vaginal irrigation with povidone-iodine, different concentrations and cleaning methods should be considered in the future.