Laparoscopic cholecystectomy has become the treatment of choice for patients with symptomatic cholelithiasis. About 10-20% of patients with gallbladder stones may also present associated common bile duct stones. The management of the latter remains controversial because many different surgical strategies are available: laparoscopic treatment (laparoscopic common bile duct exploration), sequential endoscopic and laparoscopic treatment (endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy [ERCP/ES] prior to laparoscopic cholecystectomy), inverted sequential endoscopic-laparoscopic treatment (laparoscopic cholecystectomy followed by ERCP/ES), and combined endoscopic-laparoscopic treatment (laparoscopic cholecystectomy with intraoperative ERCP/ES). The aim of this study was to evaluate the efficacy and safety of sequential endoscopic-laparoscopic treatment in patients with cholecystocholedocholithiasis. We retrospectively analyzed the clinical, biochemical and radiological features of 552 patients operated on for cholelithiasis from 1991 to 2001. Common bile duct stones were suspected on the basis of increased serum levels of bilirubin, GOT, GPT, GGT, alkaline phosphatase; presence of jaundice; history of pancreatitis or cholangitis; dilated common bile duct (diameter > 8 mm) or common bile duct stones at hepatobiliary ultrasonography; presence of common bile duct stones at MR-cholangiography or at i.v. cholangiography. In patients with suspected common bile duct stones, preoperative ERCP was performed; if common bile duct stones were confirmed, ES was performed. When common bile duct stones were not suspected preoperatively, laparoscopic cholecystectomy was performed directly. Overall morbidity, mortality and conversion rates in the two groups were evaluated. Of 552 patients admitted for cholelithiasis, 62 (11.3%) underwent preoperative ERCP for suspected common bile duct stones. In 41 patients (66.1%) common bile duct stones were identified and ES with common bile duct stone extraction was performed in 40 patients (clearance: 97.5%). The overall morbidity was 16% (10 cases of post-ERCP acute pancreatitis); no mortality occurred. The conversion rate during subsequent laparoscopic cholecystectomy was 4.8%. In the group of patients with no suspicion of common bile duct stones, the conversion rate was 4.9%. Sequential treatment cannot be considered the best approach for patients with cholecystocholedocholithiasis because of its morbidity rate and the high rate of negative preoperative ERCP findings. Combined endoscopic-laparoscopic treatment seems to present more advantages, especially in term of morbidity, hospital stay and patient compliance and may, in future, be considered the treatment of choice for patients with cholecystocholedocholithiasis.