Background and Aims Laparoscopic common bile duct exploration and endoscopic choledochectomy are still controversial in the treatment of secondary choledocholithiasis, but reports in the literature tend to be a single-stage treatment strategy of primary closure following laparoscopic common bile duct exploration combined with cholecystectomy. Therefore, this study was conducted to compare the clinical efficacy of primary suture of laparoscopic common bile duct and endoscopic stone extraction in the treatment of secondary choledocholithiasis.Methods The clinical data of 183 patients with secondary choledocholithiasis treated in the Second Department of Hepatopancreatobiliary Surgery of Tianjin Nankai Hospital from January 2019 to February 2020 were retrospectively analyzed. Of the patients, 60 cases underwent laparoscopic common bile duct exploration with primary closure plus cholecystectomy (primary closure group), and 123 cases underwent endoscopic retrograde cholangiopancreatography/endoscopic lithotomy plus laparoscopic cholecystectomy (endoscopic stone extraction group). The two groups of patients were matched using 1∶1 propensity score matching (PSM), with a total of 59 pairs successfully matched. The surgical efficacy, postoperative complications, length of hospitalization and other clinical variables after matching were compared between the two groups, and the influencing factors for length of postoperative hospital stay and associated postoperative complications were also analyzed.Results Before PSM, there was a statistical difference in sex between the two groups (P=0.007). After PSM, all differences in the baseline data of the two groups had no statistical significance (all P>0.05). The overall incidence of postoperative complication in endoscopic stone extraction group was higher than that in primary closure group (P<0.05), which was mainly due to the higher incidence rate of postoperative hyperamylasemia in the former (20.3% vs. 0). There were no statistical differences in the incidence rates of other specific complications between the two groups (all P>0.05). The length of postoperative hospital stay was shorter and the hospitalization cost was lower in primary closure group than those in endoscopic stone extraction group (both P<0.05). The old age (OR=0.396, 95% CI=0.182-0.864, P=0.020), hyperamylasemia (OR=0.057, 95% CI=0.007-0.468, P=0.008) and endoscopic stone extraction (OR=0.084, 95% CI=0.040-0.179, P=0.000) were risk factors for prolonged postoperative hospital stay, and the surgical method was an influencing factor for postoperative hyperamylasemia (P<0.05). Followed up was conducted for at least 1 year in the two groups of patients, and no stone recurrence and biliary stenosis occurred.Conclusion Compared with endoscopic stone removal, the primary closure of the laparoscopic common bile duct for the treatment of secondary common bile duct stones has the advantages of shorter hospital stay and lower cost, with no damage to the normal physiological structure of the sphincter of Oddi.