Objective To investigate therapeutic effect of endoscopic sphincterotomy with small incision (SES) combined with endoscopic papillary balloon dilation (EPBD) in treatment of larger common bile duct stones. Methods The clinical data of 80 patients with common bile duct stones treated in our hospital from February 2014 to October 2015 were retrospectively analyzed. These patients were divided into endoscopic sphincterotomy (EST) group (n = 40) and SES+EPBD group (n = 40) according to the therapeutic methods. The diameter of common bile duct stone was 10–20 mm. The operation status, recurrence rate and residual rate of common bile duct stone, and complications rate within 3 months after operation were compared between these two groups. Results The age and gender had no significant differences between these two groups (P>0.05). The operation time was shorter (P<0.05) and the intraoperative bleeding was less (P<0.05) in the SES+EPBD group as compared with the EST group. There were no significant differences in the hospital stay and recovery time of gastrointestinal function between these two groups (P>0.05). The levels of ALT, AST, DBIL, and TBIL in these two groups before treatment had no significant differences (P>0.05); after treatment, the above indicators of liver function in the SES+EPBD group were significantly lower than those in the EST group (P<0.05), and which were significantly decreased more in the same group (P<0.05). The residual stone, stone recurrence, and complications such as acute pancreatitis, acute cholangitis, bile leakage and postoperative hemorrhage were not found in the SES+EPBD group, the rates of these indicators in the SES+EPBD group were significantly lower than those in the EST group (P<0.05). Conclusion SES combined with EPBD has a good therapeutic effect on larger common bile duct stones (diameter of common bile duct stone is 10–20 mm) and recurrence rate is low.