OBJECTIVES: Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP/ES) can be associated with unforeseeable complications, especially when involving postprocedural pancreatitis. The aim of the study was to investigate risk factors for complications of ERCP/ES in a prospective multicentric study. METHODS: One hundred fifty variables were prospectively collected at time of ERCP/ES and before hospital discharge over 2 years, in consecutive patients undergoing the procedure in nine endoscopic units in the Lombardy region of Italy. More than 150 ERCPs were performed in each center per year by a single operator or by a team of no more than three endoscopists. RESULTS: Two thousand four hundred sixty-two procedures were performed; 18 patients were discharged because the papilla of Vater was not reached (duodenal obstruction, previous gastrectomy, etc.). Two thousand four hundred forty-four procedures were considered in 2103 patients. Overall complications occurred in 121 patients (4.95% of cases): pancreatitis in 44 patients (1.8%), hemorrhage in 30 (1.13%), cholangitis in 14 (0.57%), perforation during ES in 14 (0.57%), and others in 14 (0.57%); deaths occurred in three patients (0.12%). In multivariate analysis, the following were significant risk factors: a) for pancreatitis, age (< or = 60 yr), use of precutting technique, and failed clearing of biliary stones, and b) for hemorrhage, precut sphincterotomy and obstruction of the orifice of the papilla of Vater. CONCLUSIONS: The results of our study further contribute to the assessment of risk factors for complications related to ERCP/ES. It is crucial to identify high risk patients to reduce complications of the procedures.