OBJECTIVE: Assessing the efficacy of intraoperative 4-factor prothrombin complex concentrate (4F-PCC) use in blood product utilization, time to chest closure, intensive care unit (ICU) and hospital length of stay (LOS), thromboembolic complications, renal injury and mortality in left ventricular assist device (LVAD) patients on home anticoagulation therapy with warfarin, undergoing orthotopic heart transplantation (OHT). DESIGN: Retrospective analysis of OHT patients at Tufts Medical Center from May 2013 to October 2016. SETTING: Single-institution, university hospital setting. PARTICIPANTS: Patients with preexisting LVADs who received orthotopic heart transplants (n = 74; 32 patients 4F-PCC, 42 patients no 4F-PCC). INTERVENTIONS: Warfarin reversal using 4F-PCC in patients with LVADs undergoing orthotopic heart transplantation with the 4F-PCC dosing partitioned such that one-third was given pre-CPB and two-thirds were given post-CPB. MEASUREMENTS AND MAIN RESULTS: The 4F-PCC group required less plasma (6 [IQR 4] v 1.31 [IQR 2] U, p < 0.001), cryoprecipitate (10 [IQR 10] v 7.50 [IQR 5] U, p < 0.001), and packed red blood cells (5 [IQR 4] v 2 [IQR 1.5] U, p < 0.001) and had a shorter time to chest closure (618.8 ± 111.4 v 547.9 ± 110.1 minutes, p = 0.008). There was no difference in platelet transfusion (2 [IQR 1] v 2 [IQR 1] U, p = 0.16), ICU or hospital LOS, acute kidney injury, or mortality. No thrombotic complications occurred. CONCLUSIONS: Replacing plasma with 4F-PCC to reverse preoperative warfarin anticoagulation during OHT was associated with a shorter time to chest closure and less blood product utilization, without an increase in acute kidney injury, thromboembolic complications, or death.