Previous studies suggest low, fixed-dose regimens of activated prothrombin complex concentrate [factor VIII inhibitor bypassing activity (FEIBA); 500 U for international normalized ratio (INR) < 5; 1000 U for INR > 5] is effective for reversal of warfarin-induced life-threatening bleeds. Little data are available on the use of high-dose, weight-based FEIBA for this indication. The objective of this study was to evaluate effectiveness and safety of high-dose, weight-based FEIBA (50 U/kg) vs. frozen plasma alone in this population. This was a matched case–control, multicenter retrospective study including patients who received high-dose, weight-based FEIBA or frozen plasma alone for warfarin-induced life-threatening bleeds matched (1 : 1) based on age and bleed location. Forty-eight patients were included in the analysis (24 FEIBA, 24 frozen plasma). The primary endpoint was time to INR less than 1.5 after administration of FEIBA or frozen plasma. Secondary endpoints include rates of thromboembolic events and mortality. Median baseline INR was 3.7 (interquartile range 2.7, 7.30) and 2.9 (2.3, 6.61) in the FEIBA and frozen plasma groups, respectively (P = 0.13). Median FEIBA dose was 4530 (3672, 5028) U. Use of FEIBA resulted in faster time to INR less than 1.5 with a median of 2.5 (1.25, 4.15) vs. 12 (5.6, 28.35) h; (P < 0.0001). Thromboembolic events occurred in nine (16.7%) patients (FEIBA n = 5; plasma n = 4); (P = 1.0). Mortality was similar in both groups (FEIBA 33% vs. frozen plasma 15%; P = 0.2). The use of high-dose, weight-based FEIBA resulted in faster time to reversal of warfarin-induced coagulopathy compared with frozen plasma alone and showed a similar safety profile.