Background: The use of needle-knife sphincterotomy as a method of precut sphincterotomy has been criticized as potentially unsafe. Despite this, a number of tertiary referral centers have reported their successful use of this technique to increase the rate of common bile duct cannulation. Methods: We assessed the safety and efficacy of needle-knife sphincterotomy in 72 consecutive patients in whom attempts at standard common bile duct cannulation were unsuccessful. Bile duct diameters were correlated to the complication rate. Results: Cannulation of the common bile duct was successful immediately after needle-knife sphincterotomy in 50 patients (67%), and was successful in 17 of the 20 patients who underwent repeat ERCP, for a total cannulation rate of 93%. Eight patients (11%) experienced complications. Retroduodenal perforation during guide wire cannulation attempts and bleeding occurred as frequently as pancreatitis. Small duct size was a risk factor for complications. There was no procedure-related mortality, and all complications were managed medically. Conclusions: Needle-knife sphincterotomy was effective in facilitating cannulation in patients fresh sphincterotomy site and excluding patients with small duct size may further reduce the complication rate.