Objective: To evaluate the effectiveness, safety and economic value between laparoscopic cholecystectomy (LC) plus laparoscopic common bile duct exploration (LCBDE) and endoscopic sphincterotomy (EST) plus LC in treatment of common bile duct stones. Methods: Using a prospective, randomized controlled approach, patients with confirmed choledocholithiasis were randomly assigned in a 1:1 ratio to two groups to undergo LC+LCBD and EST+LC, respectively. Six-month postoperative follow-up was conducted. The main clinical variables between the two groups of patients were compared. Results: One hundred and ten patients were enrolled. In LC+LCBD group, the average operative time was (103.9±18.0) min, the average intraoperative blood loss was (15.3±29.5) mL, 3 cases (5.5%) had open conversion, the average length of hospital stay was (12.02±5.8) d and the average hospitalization cost was (32 116± 6 503) yuan, and no residual stone was found during follow-up. In EST+LC group, the average operative was (175.2±10.5) min, the average intraoperative blood loss was (6.8±7.0) mL, 2 cases (3.6%) had open conversion, the average length of hospital stay was (11.9±3.0) d, the average hospitalization cost was (37 571± 5 017) yuan, and residual stone was found in one case during follow-up. Between the two groups, the operative time, intraoperative blood loss and hospitalization cost had statistical difference (all P<0.05), while no statistical difference was noted in the remaining variables (all P>0.05). Conclusion: The two combined minimally invasive procedures show no obvious difference in effectiveness and safety. However, LC+LCBDE is preferentially recommended for its low costs.