Sg4b-5 anatomical bi-segmentectomy with regional lymphadenectomy (Sg4b5) is a surgical option for gallbladder cancer (GBC) treatment. The laparoscopic approach to this challenging operation is still controversial. Aim of this study was to compare short- and long-term outcomes of laparoscopic versus open Sg4b5 in a single institution series of patients. All consecutive patients who underwent Sg4b5 for GBC from January 2000 to September 2021 were retrospectively reviewed. Inverse probability of treatment weighting (IPTW) analysis was performed. 75 patients were analyzed, 18 in the laparoscopic and 57 in the open group. After IPTW, laparoscopic approach was associated with a significantly decreased median intraoperative blood loss (100 vs 237.09ml, p = 0.001), shorter median length of hospital stay (4 vs 8days, p = < 0.001) and a higher median number of harvested nodes (9 vs 7, p = 0.026). Operation time was shorter in the open group (355 vs 259min, p < 0.001). No significant differences were found regarding clear resection margins, overall and major (Clavien-Dindo ≥ 3) morbidity, bile leakage rate, 90days post-operative mortality, overall and disease-free survival. Laparoscopic Sg4b-5 anatomical bi-segmentectomy and regional lymphadenectomy is feasible and safe with long term outcome comparable to open approach at least in early stages. Laparoscopic approach confirms its well-known short-term benefits with less intraoperative bleeding and shorter length of stay. Moreover, it might allow a better lymphadenectomy.