Objective To study the clinical application of laparoscopic cholecystectomy (LC) combined with intraoperative endoscopic sphincterotomy (IOEST) with the antegrade guidewire technique in the treatment of cholecystocholedocholithiasis.Methods This is a prospective controlled study comparing LC combined with preoperative endoscopic sphincterotomy (POEST) versus LC combined with IOEST in the treatment of cholecystocholedocholithiasis.Patients who were diagnosed to have cholecystocholedocholithiasis from June 2012 to February 2013 in our hospital were divided into the POEST group and the IOEST group.There were 50 patients in each group.The operation time,successful stone-extraction rate,residual stones rate,complication rate,postoperative stay and hospitalization cost between the groups were compared.Results The sex,age,stone size,number of stones and diameter of the common bile duct showed no significant difference between the two groups (P ＞ 0.05).There were no differences between the two groups in surgical time of EST,surgical time of LC combined with EST,successful stone-extraction rate and hospitalization cost (P ＞ 0.05).There were significant differences between the two groups in the residual stones rate,postoperative hyperamylasemia rate,postoperative acute pancreatitis rate and postoperative stay (P ＜0.05).LC combined with IOEST using the antegrade insertion of guidewire technique significantly reduced the residual stones rate (0 vs 8％),postoperative hyperamylasemia rate (4％ vs 18％),postoperative acute pancreatitis rate (0 vs 8％) and postoperative stay.Conclusions LC combined with IOEST using the antegrade guidewire technique could be performed safely when compared with the traditional sequential technique,LC combined with IOEST using the antegrade guidewire technique significantly reduced the postoperative acute pancreatitis rate and the residual stones rate.LC combined with IOEST using the antegrade guidewire technique should be the recommended technique to treat patients with cholecystocholedocholithiasis.