Background and Aims Laparoscopic cholecystectomy combined with laparoscopic transcystic common bile duct exploration (LC+LTCBDE) and endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy combined with laparoscopic cholecystectomy (ERCP/EST+LC) both are minimally invasive procedures for the treatment of cholecystolithiasis with choledocholithiasis. However, the merits of the two procedures are still under debate. Therefore, this study was performed to compare the efficacy of the two minimally invasive procedures in the treatment of concomitant cholecystolithiasis and choledocholithiasis through a retrospective analysis.Methods The clinical data of 161 patients with concomitant cholecystolithiasis and choledocholithiasis whom been treated in the Second People's Hospital of Neijiang City from July 2017 to August 2020 were retrospectively analyzed. Of the patients, 78 cases underwent LC+LTCDBE, and 83 cases were subjected to ERCP/EST+LC. The operation success rate, residual stone rate, operative time, length of hospitalization, and incidence rates of postoperative short- and long-term complications were compared between the two groups.Results There was no significant difference in the operation success rate and residual stone rate between the two groups (both P>0.05). In LC+LTCDBE group versus ERCP/EST+LC group, the operative time was longer (156.13 min vs. 129.39 min), the length of hospitalization was shorter (8.17 d vs. 13.06 d), and the hospitalization cost was lower (17 582.68 yuan vs. 29 403.10 yuan), all the differences had a statistical significance (all P<0.001). The incidence rate short-term of bile leakage was higher (7.7% vs. 0, P=0.010), but the incidence rate of pancreatitis was lower in LC+LTCDBE group than those in ERCP/EST+LC group (1.3% vs. 8.4%, P=0.037); the incidence rate of long-term cholangitis was lower in LC+LTCDBE group than that in ERCP/EST+LC group (1.3% vs. 8.4%, P=0.037). No statistical difference was noted in stone recurrence rate between the two groups (P>0.05).Conclusion Both LC+LTCBDE and ERCP/EST+LC are safe and effective surgical approaches for concomitant cholecystolithiasis and choledocholithiasis. Moreover, LC+LTCBDE offers a shortened length of hospitalization, reduced hospitalization cost, and decreased long-term complications compared with ERCP/EST+LC. Thus, it can be regarded as the preferred choice under the same indications.