['Difficult cannulation is a well known risk for post-ERCP pancreatitis. This study evaluated the outcomes of needle-knife fistulotomy (NKF) used prior to being faced with difficult biliary cannulation.', 'Patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for the purpose of biliary endotherapy between January 2007 and December 2008 were eligible for this study; 218 patients were recruited. Biliary cannulation was performed only by a standard catheter or a pull type papillotome, without wire-guided assistance in all patients. If selective cannulation was not achieved within five cannulation attempts, NKF was performed, and the results were compared with the easy cannulation group that succeeded biliary cannulation within five attempts.', 'Needle-knife fistulotomy (NKF) was performed in 72 (33.0%) of the 218 patients. The total success rate of the ERCP was 98.2% (214/218), and for the NKF group the success rate was 94.4% (68/72). The rate of complications in patients with NKF did not increase compared to patients in the easy cannulation group (P\xa0>\xa00.05): 4.2% (3/72) versus 3.4% (5/146) for acute pancreatitis, 6.9% (5/72) versus 6.8% (10/146) for bleeding, and 1.4% (1/72) versus 0% (0/146) for perforation, respectively.'] Is early use of needle-knife fistulotomy safe in situations where difficult biliary cannulation is expected?