Background In patients with liver cancer, portal vein embolization (PVE) is recommended to promote liver growth before major hepatectomies. However, the optimal embolization strategy has not been established. Purpose To compare liver regeneration as seen at CT in participants with liver cancer, before major hepatectomies, with N-butyl-cyanoacrylate (NBCA) plus iodized oil versus standard polyvinyl alcohol (PVA) particles plus coils, for PVE. Materials and Methods In this single-center, prospective, randomized controlled trial (Best Future Liver Remnant, or BestFLR, trial; International Standard Randomized Controlled Trial Number 16062796), PVE with NBCA plus iodized oil was compared with standard PVE with PVA particles plus coils in participants with liver cancer. Participant recruitment started in November 2017 and ended in March 2020. Participants were randomly assigned to undergo PVE with PVA particles plus coils or PVE with NBCA plus iodized oil. The primary end point was liver growth assessed with CT 14 days and 28 days after PVE. Secondary outcomes included posthepatectomy liver failure, surgical complications, and length of intensive care treatment and hospital stay. The Mann-Whitney U test was used to compare continuous outcomes according to PVE material, whereas the Χ2 test or Fisher exact test was used for categoric variables. Results Sixty participants (mean age, 61 years ± 11 [standard deviation]; 32 men) were assigned to the PVA particles plus coils group (n = 30) or to the NBCA plus iodized oil group (n = 30). Interim analysis revealed faster and superior liver hypertrophy for the NBCA plus iodized oil group versus the PVA particles plus coils group 14 days and 28 days after PVE (absolute hypertrophy of 46% vs 30% [P < .001] and 57% vs 37% [P < .001], respectively). Liver growth for the proposed hepatectomy was achieved in 87% of participants (26 of 30) in the NBCA plus iodized oil group versus 53% of participants (16 of 30) in the PVA particles plus coils group (P = .008) 14 days after PVE. Liver failure occurred in 13% of participants (three of 24) in the NBCA plus iodized oil group and in 27% of participants (six of 22) in the PVA particles plus coils group (P = .27). Conclusion Portal vein embolization with N-butyl-cyanoacrylate plus iodized oil produced greater and faster liver growth as seen at CT in participants with liver cancer, compared with portal vein embolization with polyvinyl alcohol particles plus coils, allowing for earlier surgical intervention.