BACKGROUND Mechanical lithotripsy and/or stent insertion is the alternative therapeutic approach in difficult endoscopic retrograde cholangiopancreatography (ERCP) case. This study was designed to investigate the appropriate treatment for extraction of bile duct stones in difficult cases of ERCP. METHODS Between 2000 and 2008, 744 ERCP procedures were performed in 592 patients with choledocholithiasis in our endoscopy unit. The demographic features, and clinical and laboratory findings were collected from a prospectively held database. Bile duct calculi were extracted by basket and/or balloon catheter following ERCP and sphincterotomy. Patients with retained stones were regarded as difficult cases. These patients were treated with mechanical lithotripsy and those with incomplete clearance of stones underwent stent placement. RESULTS Two hundred and forty-five patients (41%) were male and 347 (59%) were female with a mean age of 58 years (range 19-95 years). Stones were impacted in 27 patients (5%). Stone extraction was performed by basket and/or balloon catheter in 610 ERCP procedures, and lithotripsy was performed in 70 ERCP procedures. Forty-four patients underwent stent insertion, and 20 underwent stent replacement. Morbidity occurred in 39 patients (5%), with no mortality associated with the procedure. Hemorrhage occurred in 9 patients and basket impaction in 4. Mild pancreatitis and cholangitis developed in 12 and 11 patients, respectively. CONCLUSIONS Difficult cases of bile duct stones can be treated successfully with lithotripsy, and a stent should be applied when the common bile duct cannot be cleared completely.