Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (ES) is the most widely used technique for treating choledocholithiasis.In some cases, due to anomalies of the papilla or the presence of large or multiple calculi, additional maneuvers are needed to remove the stones. The present study investigates the efficacy and safety of ES with sphincteroplasty (SP) in the management of choledocholithiasis with extraction difficulties. Patients and Methods: A prospective study was made of 153 patients with choledocholithiasis subjected to ERCP. Fifty-two patients underwent ES with SP, while 101 were subjected only to ES. The two groups were compared in terms of age, gender, percentage cannulation, presence of papilla alterations, large or multiple stones, success in stone removal and complications (acute pancreatitis, bleeding and perforation). In the ES with SP group, we moreover recorded the diameters of the balloons employed (10 -18 mm). Results: There were no significant differences between the groups in the stone extraction success rate (94.23% in the ES with SP group versus 97.03% in the ES group) or in the appearance of complications (3.8% in the ES with SP group versus 2.7% in the ES group). The presence of difficult papillae, and of multiple or large stones was significantly greater in the ES with SP group. The diameter of the balloon was not associated with the appearance of complications. Conclusion: Endoscopic sphincterotomy with sphincteroplasty is effective and safe in the treatment of choledocholithiasis with extraction difficulties.