Post-ERCP remains a major challenge, although significant progress has been made in predicting risk and methods of prevention. Facets of post-ERCP pancreatitis can be divided into the four "P's": they are patient-related factors, procedure-related factors, pancreatic stents, and pharmacoprophylaxis. New information about risk factors includes a description of IPMN as a patient-related risk, with smoking and chronic liver disease as protective factors. Procedure-related factors include one or more deep passages of a guidewire into the pancreatic duct as a salient risk, perhaps outweighing difficult cannulation or contrast injection, but one that can be mitigated by placement of a pancreatic stent. In addition, placement of transpapillary metallic stents has emerged as an independent risk for post-ERCP pancreatitis (PEP). Although there has been a rising wave of enthusiasm for rectal NSAIDs as a kind of panacea for prevention of post-ERCP pancreatitis, the newest data question their efficacy in unselected cohorts. Pancreatic stent placement remains the most proven and reliable method of preventing post-ERCP pancreatitis in both mixed- and high-risk ERCP. Success at placement of protective pancreatic stents is a paramount for safety and efficacy, and technical expertise at placing pancreatic stents widely among centers. The use of specialized techniques including very small caliber guidewires and stents is necessary to approach 100 % success.