IntroductionFollowing major liver resection, posthepatectomy liver failure (PHLF) is associated with a high mortality rate. As there is no therapy for PHLF available, avoidance remains the main goal. A sufficient future liver remnant (FLR) is one of the most important factors to reduce the risk for PHLF; however, it is not known which patients benefit of volumetric assessment prior to major surgery. MethodsA retrospective, bi-institutional cohort study was conducted including all patients who underwent major hepatectomy (extended right hepatectomy, right hepatectomy, extended left hepatectomy and left hepatectomy) between 2010 and 2023. ResultsA total of 1511 major hepatectomies were included, with 29.4 % of patients undergoing FLR volume assessment preoperatively. Overall, PHLF B/C occurred in 9.8 % of cases. Multivariate analysis identified diabetes mellitus, extended right hepatectomy, perihilar cholangiocarcinoma (pCCA), gallbladder cancer (GBC) and cirrhosis as significant risk factors for PHLF B/C. High-risk patients (with one or more risk factors) had a 15 % overall incidence of PHLF, increasing to 32 % with a FLR <30 %, and 13 % with an FLR of 30–40 %. Low-risk patients with a FLR <30 % had a PHLF rate of 21 %, which decreased to 8 % and 5 % for FLRs of 30–40 % and >40 %, respectively. For right hepatectomy, the PHLF rate was 23 % in low-risk and 38 % in high-risk patients with FLR <30 %. ConclusionPatients scheduled for right hepatectomy and extended right hepatectomy should undergo volumetric assessment of the FLR. Volumetry should always be considered before major hepatectomy in patients with risk factors such as diabetes, cirrhosis, GBC and pCCA. In high-risk patients, a FLR cut-off of 30 % may be insufficient to prevent PHLF, and additional liver function assessment should be considered.