Background and Aims Extra-Glissonian approach was first proposed by Japanese scholar Takasaki and used in open surgery. With the enhancement of the concept of minimal invasiveness, surgery has gradually entered into the minimally invasive era, and hepatobiliary surgeons flexibly applied the extra-Glissonian approach in laparoscopic hepatectomy. This study was conducted to compare the safety and short-term efficacy of laparoscopic extra-Glissonian approach and intra-Glissonian approach in handling the hepatic pedicle of the right posterior lobe during anatomical right posterior lobotomy through a retrospective analysis.Methods The clinical data of 43 patients who underwent laparoscopic right posterior lobotomy in Hunan Provincial People's Hospital from January 2015 to September 2019 were retrospectively analyzed. Of the patients, the extra-Glissonian approach was used to deal with the hepatic pedicle of the right posterior lobe in 29 cases (extra-Glissonian group), and the intra-Glissonian approach was used to deal with the hepatic pedicle of the right posterior lobe in 14 cases (intra-Glissonian group). The operative time, intraoperative blood loss, length of hospital stay, postoperative complications, liver function indexes (total bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase) on the third day after surgery and prothrombin time were compared between the two groups.Results There were no statistical differences in preoperative data and disease constitution (hepatocellular carcinoma was dominant type in either group) between the two groups of patients (all P>0.05). The average operative time in extra-Glissonian group was significantly shorter than that in intra-Glissonian group (191.72 min vs. 231.54 min, P=0.001), while other variables that included the intraoperative blood loss, liver function indexes and prothrombin time on the postoperative day 3, length of hospital stay and incidence of complications shortly after surgery showed no statistical differences between the two groups of patients (all P>0.05). No perioperative death occurred in both groups.Conclusion Extra-Glissonian approach and intra-glissonian approach are equally safe in laparoscopic anatomical right posterior lobectomy. However, there should be sufficient preoperative imaging data and a full understanding of the anatomical structure and variation of the intrahepatic duct. Under the premise of mastery of surgical indications and skilled operation of laparoscopic surgery, the application of the extra-Glissonian approach can shorten the operative time and improve the operation efficiency.