Background/aims: Endoscopic retrograde cholangiopancreatography has become the standard treatment for common bile duct stones worldwide. There are only a few reports with small number of patients concerning the factors that contribute to the technical difficulty of endoscopic retrograde cholangiopancreatography in these patients. In this study, we aimed to investigate these factors in a large group of patients. Materials and Methods: All patients with naive papilla (n=1850) who underwent endoscopic retrograde cholangiopancreatography during a study period of 2 years were prospectively evaluated. Among them, 757 patients with common bile duct stones were included in the study. Following successful cannulation, the patients who needed either more than one episode for stone extraction or mechanical lithotripsy, extracorporeal shock wave lithotripsy or in whom stone extraction could not be achieved endoscopically and underwent surgery were regarded as having "difficult stones". Age, sex, laboratory parameters, endoscopic and cholangiographic findings were recorded in all patients. Predictive factors for difficult stones were investigated in univariate and multivariate analysis. Results: The study group consisted of 432 women and 325 men with a mean age of 60 +/- 16 years (range, 4-96). Of the total 757 patients, 654 (86.4%) had easy and 103 (13.6%) had difficult stones. Endoscopic stone extraction was successful in 98.1% of patients. Stricture distal to the stone (OR: 8.248), smaller common bile duct/stone diameter ratio (OR: 0.348), stone diameter (OR: 1.187), stone impaction (OR: 1.117), and higher bilirubin levels (OR: 1.1) were found to be independent predictors of difficult stone in multivariate analysis. Conclusion: Endoscopic retrograde cholangiopancreatography is a very effective method for the treatment of common bile duct stones. Besides strictures distal to the stone, smaller common bile duct/stone diameter ratio, stone diameter, impacted stone, and higher bilirubin levels are significant predictors of difficult stone.