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Background: Recombinant and plasma-derived factor products, such as activated factor seven (rFVIIa) and four-factor prothrombin complex concentrate (4-factor PCC), have been used off-label for bleeding after cardiac surgery, but little evidence has been published regarding their efficacy and safety. Objective: To determine whether there is a difference in chest tube output in patients who have received 4-factor PCC or rFVIIa for critical postoperative bleeding associated with cardiovascular surgery. Methods: A retrospective chart review was conducted utilizing the electronic medical record system at a 657-bed community, tertiary care hospital in Nashville, Tennessee. Nonpregnant patients ≥18 years of age experiencing significant bleeding during cardiac surgery who received either PCC or rFVIIa perioperatively or postoperatively between April 2015 through December 2016 were eligible for inclusion. Patients were excluded if they received 4-factor PCC or rFVIIa for any indication other than bleeding during cardiac surgery or if they received both agents. Results: Data conclude that there is no significant difference in chest tube output 24 hours postoperatively between patients treated with 4-factor PCC or rFVIIa. There was no difference in bleeding, thromboembolic events, or re-exploration between the rFVIIa and 4-factor PCC groups, but there was a difference in units of fresh frozen plasma administered and hospital length of stay. Conclusion: 4-Factor PCC may be an equally efficacious alternative to rFVIIa for patients experiencing significant bleeding during cardiac surgery. There is no difference in chest tube output; therefore, there is no difference in bleeding—either at 24 hours postoperatively or total.