Objective To explore the safety and efficacy of small endoscopic sphincterotomy combined with endoscopic balloon dilatation (sEST+EPBD) for large common bile duct stones. Methods From Jan. 2012 to Dec. 2015, 167 patients suffered from large common bile duct stones were recruited to Central Hospital of Shengli Oil Field and randomly divided into EST group (n = 71) and sEST+EPBD group (n = 96). The safety and efficacy of EST and sEST + EPLBD were compared by logstic regression analysis. Results The complete stone removal ratesin of EST and sEST+EPBD were 91.5% and 92.7%, respectively (P = 0.076), and the X-ray exposure time was significantly shorter in sEST+EPBD group (P <0.001). There was no significant difference in the incidence rate of recent complications between EST and sEST+EPBD groups (P = 0.221), however, the incidence of bleeding and long-term complications in the sEST+EPBD group was significantly lower (P = 0.018, 0.028, accordingly). Bile duct stone diameter was a factor influenced both successful stone removal and post-ERCP pancreatitis. Conclusions Both EST and sEST+EPBD are approximately equivalent in terms of successful clearance of large common bile duct stones, the complications in two groups are different. Therefore, it is necessary to select the optimal surgical project according to the actual clinical situation.