Simple SummaryLaparoscopic right hemihepatectomy (L-RHH) after future liver remnant modulation (FLRM) is considered a technically challenging procedure. This study included consecutive L-RHHs performed by a single surgeon, both with and without prior FLRM. The analysis included 59 patients who underwent L-RHH between October 2007 and March 2023, of which 33 patients received FLRM. L-RHH after FLRM was more technically challenging, as it required longer operative time and Pringle duration. However, there were no significant differences in intraoperative blood loss, conversion rates, or postoperative outcomes such as hospital stay, morbidity rates, and textbook outcome. When performed by experienced laparoscopic hepatobiliary surgeons, L-RHH after FLRM is a safe and feasible procedure.AbstractBackground: Laparoscopic right hemihepatectomy (L-RHH) is still considered a technically complex procedure, which should only be performed by experienced surgeons in specialized centers. Future liver remnant modulation (FLRM) strategies, including portal vein embolization (PVE), and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), might increase the surgical difficulty of L-RHH, due to the distortion of hepatic anatomy, periportal inflammation, and fibrosis. Therefore, this study aims to evaluate the safety and feasibility of L-RHH after FLRM, when compared with ex novo L-RHH. Methods: All consecutive right hemihepatectomies performed by a single surgeon in the period between October 2007 and March 2023 were retrospectively analyzed. The patient characteristics and perioperative outcomes of L-RHH after FLRM and ex novo L-RHH were compared. Results: A total of 59 patients were included in the analysis, of whom 33 underwent FLRM. Patients undergoing FLRM prior to L-RHH were most often male (93.9% vs. 42.3%,p< 0.001), had an ASA-score >2 (45.5% vs. 9.5%,p= 0.006), and underwent a two-stage hepatectomy (45.5% vs. 3.8%p< 0.001). L-RHH after FLRM was associated with longer operative time (median 360 vs. 300 min,p= 0.008) and Pringle duration (31 vs. 24 min,p= 0.011). Intraoperative blood loss, unfavorable intraoperative incidents, and conversion rates were similar in both groups. There were no significant differences in length of hospital stay and 30-day overall and severe morbidity rates. Radical resection margin (R0) and textbook outcome rates were equal. One patient who underwent an extended RHH in the FLRM group deceased within 90 days of surgery, due to post-hepatectomy liver failure. Conclusion: L-RHH after FLRM is more technically complex than L-RHH ex novo, as objectified by longer operative time and Pringle duration. Nevertheless, this procedure appears safe and feasible in experienced hands.