Background: Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred technique for treating pathologies of the bile duct. It has been suggested that this procedure, combined with sphincterotomy, may influence the subsequent development of long-term complications. The main objective of this study was to determine the long-term complications of biliopancreatic disease after ERCP and their potential association with the development of biliopancreatic neoplasms. Methods: This retrospective cohort study included 576 patients who underwent ERCP (referred to as index ERCP) with sphincterotomy for benign biliary disease, with a minimum follow-up period of more than 2 years. Results: The incidence of long-term benign and neoplastic pathologies after ERCP was analyzed. The most common findings were recurrence of choledocholithiasis in 70 patients (12.1%), cholangitis “sine materia” in 27 patients (4.7%), and acute pancreatitis in 8 patients (1.4%). Eight patients (1.4%) developed hepatobiliopancreatic neoplasms, including 4 cases of pancreatic neoplasms (0.7%), 1 cholangiocarcinoma (0.2%), 1 ampulloma (0.2%), and 2 intrahepatic neoplasms (0.3%). Multivariate analysis revealed that factors such as age over 50 years, previous biliary surgery, diversion of the bile duct (BD) to the digestive tract, dilation of the BD, stent placement, biopsy, and cholecystectomy were factors associated with an increased risk of long-term benign complications. Conclusion: Endoscopic retrograde cholangiopancreatography with sphincterotomy is associated with an increased long-term risk of subsequent benign biliopancreatic disease. However, our data do not allow us to establish a direct relationship with the development of biliopancreatic neoplasms. Cite this article as: Ibáñez M, López C, Trujillo J, Ramón Gómez J, Vaquero Puerta C, Carlos Martin del Olmo J. Long-term risks of benign and malign complications after endoscopic sphincterotomy in the management of benign biliopancreatic pathology: A cohort study. Eurasian J Med., 2024;56(1):1-6