OBJECTIVE: To compare the safety and efficiency of preoperative endoscopic sphincterotomy (POES) versus intraoperative endoscopic sphincterotomy (IOES) in patients with gallbladder and common bile duct stones. METHODS: Multiple electronic databases were searched for prospective, randomized, controlled trials on the safety and effectiveness of POES versus IOES. And the outcome parameters of clearance rate, post-procedural complications and hospital stay were analyzed. RESULTS: Five trials with 631 patients (POES, n = 318; IOES, n = 313) were analyzed. Although the overall rates of common bile duct stone clearance were similar between POES and IOES (RR 0.96, 95% CI: 0.91-1.01; P = 0.13), the failure rate of CBD cannulation was significantly higher for IOES (RR 2.54, 95% CI: 1.23-5.26; P = 0.01) during endoscopic retrograde cholangiopancreatography (ERCP). The pooled RR after POES for overall complication rates was similar to that for IOES (RR 1.56, 95% CI: 0.94-2.59; P = 0.09). However, as compared with IOES, the RR risk of ERCP-related complications was significantly higher for POES (RR 2.27, 95% CI: 1.18-4.40, P = 0.01). No significant inter-group differences existed in morbidity after laparoscopic cholecystectomy or subsequent conversion into open surgery. In subgroup analyses, the rates of hemorrhage, perforation, cholangitis, cholecystitis, and gastric ulceration showed no significant inter-group differences. CONCLUSION: With regards to stone clearance and overall complication rate, POES is comparable to IOES in patients with gallbladder and common bile duct stones. However, IOES has a lowered incidence of ERCP-related pancreatitis and a shorter hospital stay