ObjectiveEven though enhanced recovery after surgery (ERAS) has been applied to liver resection worldwide, there is a lack of evidence covering its feasibility in laparoscopic major hepatectomy. This study aimed to preliminarily evaluate the superiority of ERAS in major liver resection. MethodsThe data were collected from patients who underwent laparoscopic major hepatectomy from July 2014 to November 2020 in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. The baseline characteristics, pathological features, surgical outcomes, medical costs, and postoperative pain scores were compared before and after propensity score matching (PSM). The patients were divided into the ERAS group and the routine group based on the treatment protocols. ResultsEighty-one patients who underwent laparoscopic major hepatectomy were retrospectively enrolled in the study. Before PSM, there were differences in pathology (p = 0.037) and surgical extent (p = 0.011) between the ERAS group (n = 42) and routine group (n = 39). After PSM, 26 patients from each group were matched. For surgical outcomes, patients in the ERAS group had a significantly lower postoperative complication incidence than patients in the routine group (28.6% vs. 53.8%, RR: 0.531 [0.303, 0.929], p = 0.021) before PSM. However, after PSM, superiority was not observed in the ERAS group (30.8% vs. 53.8%, RR: 0.571 [0.290, 1.13], p = 0.092). The duration of abdominal tube retention (before PSM: 5.0 d vs. 10.0 d, p < 0.001; after PSM: 6.0 d vs. 9.0 d, p = 0.001), the duration of urinary tube retention (before PSM: 1.0 d vs. 2.0 d, p < 0.001; after PSM: 1.0 d vs. 2.0 d, p = 0.002), and hospital stay (before PSM: 6.0 d vs. 11.0 d, p < 0.001; after PSM: 7.0 d vs. 11.5 d, p < 0.001) was significantly shorter in the ERAS group than in the routine group. A significant benefit on postoperative day 3 (2 vs. 3, p = 0.038) was observed with respect to the alleviation of pain after PSM. ConclusionsOur preliminary study revealed the superiority of ERAS in the setting of major liver resection, although further investigations in a large number of patients from multiple institutions are needed to evaluate the feasibility of ERAS.