Background: Increasingly, pancreatic stents are being placed to prevent post-ERCP pancreatitis. However, guidewire and stent placement may fail if the duct is small or tortuous, potentially exacerbating the risk. This study assessed the impact of unsuccessful pancreatic stent placement on complications and the efficacy of a modified technique for stent insertion when pancreatic ductal anatomy makes stent insertion technically difficult. Methods: Technical variables and 30-day complications of consecutive therapeutic ERCPs, including attempted major papilla pancreatic stent insertion were prospectively studied. Success rates for pancreatic stent placement were compared for a 1-year period during which conventional deep guidewire insertion was used and another 1-year period in which a modified technique was used as needed in patients with ductal anatomy that made stent placement technically difficult. In the modified technique, a short (2-3 cm) small diameter (3F-5F) stent was placed over a 0.018-in nitinol-tipped guidewire, passed as little as 1 to 2 cm beyond the pancreatic sphincter. Results: In 225 high-risk therapeutic ERCPs, pancreatitis occurred after the procedure in two of 3 (66.7%) patients in whom pancreatic stent insertion failed vs. 32 of 222 (14.4%) patients with successful insertion (p = 0.06). Severe pancreatitis occurred only after unsuccessful stent insertion. Significant multivariate risk factors for post-ERCP pancreatitis were unsuccessful pancreatic stent insertion (odds ratio 16.1: 95% CI[1.3, 200]), sphincter of Oddi dysfunction (odds ratio 3.2: 95% CI[1.4, 7.5]), and prior post-ERCP pancreatitis (odds ratio 3.2: 95% CI[1.4, 7.1]). The following were not risk factors: performance of pancreatic, biliary, or needle-knife pre-cut sphincterotomy; number of pancreatic contrast injections; and difficult cannulation. Stent placement was unsuccessful in 3 (3.2%) of 93 attempts during the 1-year period in which a conventional technique was used vs. none of 132 attempts in a subsequent year in which the modified technique was used. Conclusions: Failed attempts at pancreatic stent placement are associated with an extremely high risk of post-ERCP pancreatitis. Success can be consistently achieved by use of a modified technique.