Objective: To analyze the risk factors for surgical site infection after surgical treatment of hepatolithiasis, and provide effective preventive measures to reduce this problem. Methods: The clinical data of 117 hepatolithiasis patients undergoing surgical treatment from July 2005 to December 2012 were retrospectively analyzed. The patients were firstly divided, according to whether they received the special perioperative management for prevention of postoperative surgical site infection, into special treatment group and conventional treatment group, and the incidence of postoperative surgical site infection along with other clinical parameters were compared between the two groups; next, the patients were divided, according to whether they had surgical site infection, into infection group and non-infection group, and the risk factors for postoperative surgical site infection were analyzed. Results: Compared with conventional treatment group, the incidence of postoperative surgical site infection was significantly decreased (14.6% vs. 36.8%), time to drainage tube removal and length of time of antibiotic administration and postoperative stay were significantly shortened, and hospitalization cost was significantly reduced in special treatment group (all P<0.05). The univariate analysis showed that postoperative surgical site infection was associated with age, concomitant diabetes, preoperative cholangitis, previous history of biliary surgery, positive bile culture, intraoperative preventive measures, operative time and drainage tube retention time (all P<0.05); further multivariate analysis identified that concomitant diabetes, previous history of biliary surgery and long drainage tube retention time were risk factors, while implementation of intraoperative preventative measures was protective factor for postoperative surgical site infection. Conclusion: Concomitant diabetes, previous history of biliary surgery and long drainage tube retention time are independent risk factors for postoperative surgical site infection, while implementation of intraoperative preventive measures can reduce incidence of surgical site infection and is beneficial to fast recovery of the patients.