Introduction: Excessive bleeding after cardiac surgery is a major complication associated with increased morbidity and mortality. Intraoperative use of plasma-derived coagulation factors, such as four-factor prothrombin complex concentrate (4F-PCC), have been introduced into clinical practice to attenuate adverse effects attributable to postoperative hemorrhage. Although recent literature reports positive outcomes with the use of lower, fixed doses of 4F-PCC for emergent anticoagulation reversal, there is a paucity of literature evaluating fixed dosing in the cardiac surgery setting. The purpose of this study is to compare the rates of moderate- or higher severity postoperative bleeding associated with use of a fixed-dose versus weight-based 4F-PCC dosing strategy in cardiac surgery patients. Methods: A retrospective cohort study was performed of adult patients who received either weight-based (25 IU/kg) or fixed-dose (1500 IU) 4F-PCC during a cardiac surgical procedure over a 2-year period. Bleeding outcomes were determined by postoperative blood product transfusion requirements, chest tube output volume, and the need for surgical reexploration due to bleeding complications. Results: Of the 122 patients included, 58 received weight-based 4F-PCC whereas 62 were managed with a fixed-dose strategy. Rates of moderate- or higher severity bleeding were similar between weight-based and fixed dosing groups (56.9% vs. 46.8%, respectively; χ2 = 3.8467, p = .278) despite the use of significantly lower total 4F-PCC doses in the fixed-dose 4F-PCC cohort (25.5 U/kg vs. 21.6 U/kg; z = -2.11, p = .04). Postoperative deep vein thrombosis occurred more frequently in the weight-based dosing group as compared to the fixed-dose cohort (8.6% vs. 0%; p = .02). Conclusions: Compared to a weight-based dosing strategy, intraoperative administration of fixed-dose 4F-PCC was associated with similar postsurgical bleeding outcomes and lower rates of deep vein thrombosis in postoperative cardiac surgery patients. Larger, prospective studies are needed to validate these findings and further evaluate the impact of fixed-dose 4F-PCC on patient-centered outcomes in the postoperative cardiac surgery population.