BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is now the exclusive endoscopic therapeutic modality for biliary as well as pancreatic diseases. The aim of the present study was to investigate patient- and procedure-related risk factors for post-ERCP complications in a large-scale study of procedures performed by a single experienced endoscopist.METHODS: This is a retrospective cohort study which included a total of 2,715 therapeutic ERCPs enrolled in the final analysis. Potential important patient- and procedure-related risk factors for overall post-ERCP complications, pancreatitis and post-endoscopic sphincterotomy (ES) bleeding were investigated by univariate and multivariate analyses.RESULTS: Following the first therapeutic ERCP, 327 patients suffered complications; pancreatitis was observed in 132 (4.9%) patients, hemorrhage in 122 (4.5%) patients, cholangitis in 63 (2.3%) patients, perforation in 3 (0.11%) patients, and basket impaction in 7 (0.26%) patients. History of acute pancreatitis was more common in patients with post-ERCP complications (P<0.001). Female gender, young age (<40 years), periampullary diverticulum, suspected sphincter of Oddi dysfunction, metal stent placement, opacification of main pancreatic duct and suprapapillary fistulotomy were not found to be risk factors for overall post-ERCP complications and post-ERCP pancreatitis (PEP). Multivariate analysis showed a history of acute pancreatitis, difficult cannulation, needle-knife papillotomy, transpancreatic sphincterotomy, opacification of first and second class pancreatic ductules and acinarization as independent risk factors for overall complications and PEP, whereas antiplatelet and anticoagulation drug use were not found to be independent risk factors for post-ES bleeding.CONCLUSIONS: The results of this study demonstrate that the endoscopist's experience reduces patient- and procedure-related risk factors for post-ERCP complications.