Background: Although needle knife precut papillotomy and needle knife fistulotomy have been considered useful alternatives for achieving selective biliary cannulation, controversies remain regarding the technical proficiency for performing this procedure and safety concerns. Aim: This retrospective study evaluates the feasibility and safety of combining needle knife precut papillotomy and fistulotomy (NKPPF) to assist endoscopic retrograde cholangiopancreatography (ERCP) for difficult biliary cannulation. Methods: Data were collected and analyzed for 48 patients who underwent NKPPF between January 2008 and September 2012 at our center. The operation success rate, mean procedure time, and post-ERCP complications were investigated and compared with those of standard cannulation. Results: The success rate for NKPPF was 96% (46/48) and the mean procedure time was 4.5 ± 1.6 min based on our data set. The major complications included pancreatitis, which occurred in 2 of the 48 patients (4%), and acute cholangitis, which was observed in 1 patient (2%). There was no significant difference between the complication rate of NKPPF (6%) and standard cannulation therapeutic ERCP (4%). Conclusion: NKPPF is an effective method for accessing the biliary system after failed standard cannulation and is not associated with an increased risk of complications.