Aim: This study aims to analyze the efficacy and safety of the combination of laparoscope and preoperative (PODL) or intraoperative (IODL) duodenoscope in the treatment of cholecystolithiasis with choledocholithiasis. Materials and Methods: From January 2015 to February 2017, 51 patients with cholecystolithiasis and choledocholithiasis, who were treated with the PODL (n = 29) or IODL (n = 22), were reviewed retrospectively. The efficacy and safety were evaluated and compared between these two groups. Results: The success rates were 100% in IODL group and 96.6% in PODL group. There was no statistical significance in the difference of stone clearance rate and residual stone rate between two groups (P > .05). There were no significant differences in complications, like aspiration, gastrointestinal perforation, and acute cholangitis between two groups (P > .05). IODL significantly decreased numeric rating scale (NRS) scoring, reduced surgery cost and shortened hospitalization time compared to that of PODL group (P < .05). No cholangitis, reoccurrence of stones or biliary obstruction occurred in all 51 patients. Conclusion: In this retrospective study, IODL was found superior to PODL. And the IODL can significantly decrease NRS scoring, reduce surgery cost and shorten hospitalization time.