Background: Four factor prothrombin complex (PCC4), a concentrate of factors II, VII, IX, X and protein C and S, has been used selectively for reversal of oral anticoagulation prior to surgery. There is data to support PCC4 as opposed to supplemental fresh frozen plasma (FFP) to manage postoperative bleeding following cardiac surgery. The preemptive, intraoperative use of PCC4 in cardiothoracic surgery has not been studied though it may prevent postoperative bleeding, the need for blood transfusion and the risk of transfusion related acute lung injury, volume overload, and right ventricular (RV) heart failure. The purpose of this study is to evaluate the intraoperative administration of PCC4 to decrease bleeding and lower the rate of blood transfusion. Methods: A single institution retrospective chart review conducted from May 2020 to November 2021 of patients who received PCC4 intraoperatively during cardiothoracic surgery of high risk variety. Patients were evaluated for type of surgery, demographics, baseline anticoagulation, PCC4 dose, type and quantity of blood transfusion within 72 hours postoperatively, chest tube output, incidence of right ventricular failure, hypersensitivity reactions, acute kidney injury, thrombosis, acute lung injury, and mortality within 45 days of the operative dose of PCC4. Results: Thirty five patients received PCC4 at a mean dose of 2920 units. Sixty five percent of cases were LVAD or heart transplant. The protocol is to use PCC4 30 units/kilogram immediately after completion of protamine administration. Inclusion criteria are: cardiothoracic surgery with increased risk of postoperative right heart failure commonly secondary to blood product transfusion, or cardiothoracic surgery associated with increased risk of bleeding, including: heart transplant, LVAD implant, aortic dissection, and redo sternotomy (e.g. coronary artery bypass). Total chest tube output was recorded as a mean of 757 mL for 24 hours after surgery (32 ml/hr). Overall median event rates of fresh frozen plasma (FFP) and red blood cell (RBC) transfusion were 0 (interquartile range 0 - 3 units) and 4 (interquartile range 2-5 units). Overall, forty-three percent and eighty-nine percent of cases received FFP and RBC, respectively. There was one occurrence of right ventricular failure, one occurrence of acute kidney injury requiring renal replacement therapy, one occurrence of venoarterial extracorporeal membrane oxygenation, one occurrence of venous thromboembolism related to a central venous access line, and one death unrelated to surgery or PCC4 that was attributed to advanced heart failure not amenable to advanced therapies. Conclusion: Overall patients received a low rate of blood transfusion, had minimal chest tube output, and there was a small incidence of right heart failure. Patients did not have an increased risk of adverse effects such as acute kidney injury or venous thromboembolism. A randomized controlled clinical trial comparing the observed dose and timing of PCC4 versus routine postoperative bleeding management with blood product transfusion is recommended.