Background Liver surgery after radioembolization (RE) entails highly demanding and challenging procedures due to the frequent combination of large tumors, severe RE-related adhesions, and the necessity of conducting major hepatectomies. Laparoscopic liver resection (LLR) and its associated advantages could provide benefits, as yet unreported, to these patients. The current study evaluated feasibility, morbidity, mortality, and survival outcomes for major laparoscopic liver resection after radioembolization. Material and methods In this retrospective, single-center study patients diagnosed with hepatocellular carcinoma, intrahepatic cholangiocarcinoma or metastases from colorectal cancer undergoing major laparoscopic hepatectomy after RE were identified from institutional databases. They were matched (1:2) on several pre-operative characteristics to a group of patients that underwent major LLR for the same malignancies during the same period but without previous RE. Results From March 2011 to November 2020, 9 patients underwent a major LLR after RE. No differences were observed in intraoperative blood loss (50 vs. 150 ml; p = 0.621), operative time (478 vs. 407 min; p = 0.135) or pedicle clamping time (90.5 vs 74 min; p = 0.133) between the post-RE LLR and the matched group. Similarly, no differences were observed on hospital stay ( median 3 vs. 4 days; p = 0.300), Clavien-Dindo = III complications (2 vs. 1 cases; p = 0.250), specific liver morbidity (1 vs. 1 case p = 1.000), or 90 day mortality (0 vs. 0; p = 1.000). Conclusion The laparoscopic approach for post radioembolization patients may be a feasible and safe procedure with excellent surgical and oncological outcomes and meets the current standards for laparoscopic liver resections. Further studies with larger series are needed to confirm the results herein presented.