Acute pancreatitis still represents the most common complication after procedures involving Vater's papilla; the reported incidence of this complication varies from less than 1% up to 40%. Attempts at preventing post-ERCP pancreatitis have been carried out using technical measures, pharmacological prophylaxis, or patient selection. Balloon sphincter of Oddi dilatation, difficult papillary cannulation, pancreatic sphincterotomy and multiple pancreatic duct injections have been found to be risk factors for postprocedure pancreatitis. Therefore, technique-related prevention of post-ERCP pancreatitis includes careful pancreatic duct injection, avoiding cannulation trauma, and maintaining adequate pancreatic drainage after the ERCP procedure. Pancreatic stent placement has been shown to be the most effective technique-related prevention of postprocedure pancreatitis. Apart from technique-related risk factors, operator experience also seems to be a potential risk-factor for post-ERCP/ES complications. The experience of the endoscopist rather than other patient- or technique-related conditions could probably constitute the major risk factor for postprocedure pancreatitis. Pharmacological prevention of pancreatitis after ERCP or sphincterotomy has been the topic of several investigations in recent years but still remains a debated question. Pharmacological prevention has been mainly aimed at either reducing the amount of intrapancreatic enzymes, preventing intra-cellular co-localization of enzymes and lysosomal hydrolases or blocking some steps of the enzyme-activated inflammatory cascade. Somatostatin, octreotide, gabexate mesilate and, more recently, recombinant interleukin-10 have been the most investigated drugs. Somatostatin, gabexate mesilate and recombinant interleukin-10, but not octreotide, have been found to be able to prevent post-ERCP pancreatitis in non-selected cases; however, a strategy of routine pharmacological prophylaxis in all patients is not likely to be cost-effective. A strategy of pharmacological prevention only in high-risk cases is cost-effective, but, up to now, only recombinant interleukin-10 has been proven effective. The "on demand" postprocedure treatment should also be of paramount importance, but no data are at present available regarding the potential efficacy of some drugs; on the basis of the mechanism of action, we can argue that recombinant interleukin-10 could be the only drug candidate for such a strategy. Post-ERCP pancreatitis can also be prevented by patient selection. Patient-related risk factors are now well-known, so an increased risk of developing pancreatitis is predictable "a priori" in these subjects, independently of the type of endoscopic procedure performed. Furthermore, the risk of pancreatitis escalates when multiple risk factors occur in the same patient or some technique-related risk factor comes up during the procedure. In these patients diagnostic ERCP should be avoided in routine practice and magnetic resonance cholangio-pancreatography should be used as the first diagnostic step. When either diagnostic or therapeutic ERCP is indicated, these high-risk patients should be informed about their own specific risk of postprocedure pancreatitis.