Background: A variety of factors have been linked to post-ERCP pancreatitis. However, the role of biliary stenting has not been well studied. Objective: To evaluate the relationship between biliary stenting and post-ERCP pancreatitis. Design: Prospective study of all patients undergoing ERCP with biliary stenting over a 7.5-year period. All patients had follow-up at 24 to 48 hours after the procedure and at 1 month. Setting: A single-center tertiary referral academic medical center. Patients: Consecutive patients undergoing ERCP over a 7.5-year period. Interventions: Endoscopic therapy based on the indication for and findings of ERCP. Main Outcome Measurements: The rate of post-ERCP pancreatitis. Results: A total of 3499 patients underwent ERCP with bile duct stent placement of a native papilla performed in 660: 544 (83%) 10F and 116 (17%) 7F. The most common indication for stent placement was pancreaticobiliary malignancy in 250 patients (37%). The overall rate of pancreatitis for the entire cohort was 3.17%. Multivariate analysis identified 6 factors that were associated with pancreatitis: previous ERCP pancreatitis (odds ratio [OR], 2.44; 95% CI, 1.31-4.55), age (OR, 2.30; 95% CI, 1.44-3.67), history of acute pancreatitis (OR, 1.78; 95% CI, 1.12-2.88), pancreatic sphincterotomy (OR, 2.30, 95% CI, 1.43-3.70), suspected sphincter of Oddi dysfunction (OR, 3.91; 95% CI, 2.36-6.46), and bile duct stenting (OR, 1.72; 95% CI, 1.03-2.88). The rates of pancreatitis were not significantly different based on performing sphincterotomy before stent placement, stent type, stent length, stent size, or indication. Limitations: Single-center study. Conclusions: Bile duct stent placement is an independent predictor for pancreatitis, and pancreatitis is not related to performing sphincterotomy before stenting or to stent characteristics. © 2010 American Society for Gastrointestinal Endoscopy.