Objective: To investigate the efficacy and safety of using “three-step method” to determine the timing for laparoscopic cholecystectomy (LC) following endoscopic sphincterotomy (EST) in treatment of simultaneous cholecystolithiasis and choledocholithiasis. Methods: Patients who had been definitely diagnosed with concomitant gallbladder and common bile duct stones during December 2012 to December 2017 were selected and randomly allocated into study group and control group. Patients in both groups underwent endoscopic retrograde cholangiopancreaticography (ERCP) and EST after completion of the preoperative preparation. Time interval for following LC in study group was determined by using the “three-step method” in study group, while LC was performed after the complete disappearance of clinical symptoms and the full recovery of all laboratory test results in control group. Results: A total of 116 patients were consented for the study, with 58 patients each in both groups. The baseline data were comparable between the two groups. In study group compared with control group, the length of hospital stay [12.0 (11.0–15.0) d vs. 16.5 (13.0–19.8) d, P<0.01] and total hospitalization cost [ (28 000±7 000) yuan vs. (32 000±8 000) yuan, P=0.004]were significantly reduced (both P<0.05), but the LC conversion rate, operative time, intraoperative blood loss and incidence of postoperative complication showed no significant differences (all P>0.05). Conclusion: Using “three-step method” to determine the optimal timing for LC according to the intra- and postoperative conditions of ERCP/EST can effectively reduce the length of hospital stay and hospitalization cost, and meanwhile, it has similar efficacy and safety to those by conventional method.