Postendoscopic retrograde cholangiopancreatography pancreatitis is a common and potentially devastating complication of endoscopic retrograde cholangiopancreatography. Advances in risk-stratification, patient selection, procedure technique, and prophylactic interventions have substantially improved the ability to prevent this complication. This article presents the evidence-based approaches to preventing postendoscopic retrograde cholangiopancreatography pancreatitis and discusses timely research questions in this important area.