Objective To evaluate the efficacy and safety of small-middle endoscopic sphincterotomy combined with endoscopic papillary balloon dilation for patients with extrahepatic bile duct stone. Methods The patients with special duodenal papilla included 38 cases, and those with normal duodenal papilla 143 cases. 38 patients had received SEST + EPBD, 143 had received MEST + EPBD. Results 181 patients had received SMEST + EPBD in our hospital and the related data were retrospectively analyzed. All 181 patients were successfully removed, the success rate was 100.00 %. There was no perforation occurred postoperatively, but mild acute pancreatitis occurred in 8 patients (4.42 %, 8/181) and bleeding occurred in 9 patients. The three major early complications rate were 9.93 %(17/181), which was cured by the conservative management. Conclusion SMEST plus EPBD is a safe and effective treatment for extrahepatic bile duct stone, with retaining the feature of sphincter of duodenal papilla, especially for patients with special duodenal papilla.