BACKGROUND: Pancreatitis remains the most common and feared complication of therapeutic endoscopic cholangiopancreatography (ERCP) associated with substantial morbidity. The patient-related and procedure-related independent risk factors for post-ERCP pancreatitis (PEP) in a large case volume by a single experienced endoscopist have been investigated only by few studies. The aim of the study was to investigate patient-related and procedure-related risk factors for PEP collected by a defined protocol on patients who underwent therapeutic ERCP in a single endoscopic unit during the last 8 years.PATIENTS AND METHODS: Our retrospective cohort study included a total of 2688 therapeutic ERCPs enrolled in the final analysis. The impact of the risk factors on PEP development was investigated by univariate and multivariate analysis. PEP was diagnosed and its severity was graded according to the consensus criteria.RESULTS: With the exception of history of pancreatitis, there was no other statistically significant difference of patients' characteristics between patients with and without PEP. Female sex, age, difficult cannulation, suspected sphincter of Oddi dysfunction, metal stent placement, opacification of main pancreatic duct, and suprapapillary fistulotomy were not found to be risk factors for PEP by univariate and multivariate analysis. Both univariate and multivariate analysis showed history of acute pancreatitis, needle-knife papillotomy, transpancreatic sphincterotomy, opacification of first-class and second-class pancreatic ductules, and acinarization as independent risk factors for PEP.CONCLUSIONS: History of acute pancreatitis, needle-knife papillotomy, transpancreatic sphincterotomy, opacification of first-class and second-class pancreatic ductules, and acinarization were all identified as independent risk factors for PEP.