Background: Various surgical methods are available for cholecystolithiasis plus choledocholithiasis. The objective of this study is to explore the association between laparoscopic methods and clinical outcomes of cholecystolithiasis plus choledocholithiasis. Methods: This cohort study retrospectively included patients who underwent laparoscopic surgery for cholecystolithiasis plus choledocholithiasis at our hospital (January 2017 to March 2021). The primary outcome was bile leakage. Results: Totally 127 patients were enrolled. The time to get out of bed and the indwelling duration of the abdominal drainage tube in the patients who underwent laparoscopic cholecystectomy + lithotomy of common bile duct + common bile duct primary suture + endoscopic nasobiliary drainage were higher than the endoscopic retrograde cholangiopancreatography + laparoscopic cholecystectomy group, without differences in the laparoscopic common bile duct exploration group (all P < .05). All indexes decreased in the 3 groups after surgery (all P < .01). On the first day after surgery, only white blood cells ( P < .001) and gamma-glutamyl transferase ( P = .045) showed significant differences among the different surgical methods. The incidence of biliary leakage ( P = .001) was higher in laparoscopic cholecystectomy + lithotomy of common bile duct + common bile duct primary suture + endoscopic nasobiliary drainage, while the occurrence of hyperamylasemia was higher with endoscopic retrograde cholangiopancreatography + laparoscopic cholecystectomy ( P = .001). Compared with laparoscopic cholecystectomy + lithotomy of common bile duct + common bile duct primary suture + endoscopic nasobiliary drainage, laparoscopic common bile duct exploration was associated with fewer bile leakage (RR = 0.03, 95% CI: 0.003-0.37). Conclusion: Compared with laparoscopic cholecystectomy + lithotomy of common bile duct + common bile duct primary suture + endoscopic nasobiliary drainage, laparoscopic common bile duct exploration was associated with bile leakage.