Background and Aims Hepatectomy is one of the main treatment methods for hepatolithiasis. However, the advantages of laparoscopic left-sided hepatectomy (LLH) over open left-sided hepatectomy (OLH) are still controversial. Therefore, this study was performed to compare the clinical efficacy of LLH and OLH in the treatment of hepatolithiasis using propensity score matching method.Methods The clinical data of 331 patients with hepatolithiasis who underwent left hepatectomy (including left lateral hepatectomy and left hemihepatectomy) in the First Affiliated Hospital of Nanchang University from January 2016 to July 2021 were retrospectively analyzed. The patients undergoing laparoscopic surgery (LLH group) and open surgery (OLH group) were matched by PSM at a 1:1 ratio. Main clinical variables were compared between the two groups after match.Results A total of 124 pairs of patients in the two groups were successfully matched after PSM. In LLH group compared with OLH group, the intraoperative blood loss (230.6 mL vs. 326.5 mL) and the overall incidence of complications (9.7% vs. 23.4%) were significantly decreased, and the time to restore food intake (1.9 d vs. 2.6 d), the time to regain ambulation (1.7 d vs. 2.3 d), the length of postoperative hospitalization (8.8 d vs. 10.2 d) and the total hospitalization cost (43 200 yuan vs. 57 000 yuan) were significantly reduced (all P<0.05). There were no significant differences in operative time, number of cases requiring intraoperative blood transfusion, method for common bile duct stone extraction, stone clearance rate, and stone recurrence rate between the two groups (all P>0.05). There was no reoperation and perioperative death in both groups. The open conversion rate in LLH group was 4.0%.Conclusion LLH is a safe and effective treatment for patients with left-sided hepatolithiasis, and it is superior to OLH in terms of intraoperative blood loss, overall complication, and hospitalization cost.