To determine the efficacy and safety of meticulous cannulation by needle-knife.Three needle-knife procedures were used to facilitate cannulation in cases when standard cannulation techniques failed. A total of 104 cannulations via the minor papilla attempted in 74 patients at our center between January 2008 and June 2014 were retrospectively reviewed.Standard methods were successful in 79 cannulations. Of the 25 cannulations that could not be performed by standard methods, 19 were performed by needle-knife, while 17 (89.5%) were successful. Needle-knife use improved the success rate of cannulation [76.0%, 79/104 vs 92.3%, (79 + 17)/104; P = 0.001]. When the 6 cases not appropriate for needle-knife cannulation were excluded, the success rate was improved further (80.6%, 79/98 vs 98.0%, 96/98; P = 0.000). There were no significant differences in the rates of post-endoscopic retrograde cholangiopancreatography adverse events between the group using standard methods alone and the group using needle-knife after failure of standard methods (4.7% vs 10.5%, P = 0.301).The needle-knife procedure may be an alternative method for improving the success rate of cannulation via the minor papilla, particularly when standard cannulation has failed.