Perioperative hemorrhage during cardiac surgery is a frequent occurrence and can result in significant morbidity and mortality for patients. Prothrombin complex concentrate (PCC) and recombinant factor VIIa (rFVIIa) are therapies that have been used extensively in cardiac surgery with some promise, but with some concern around acute kidney injury (AKI) and thromboembolic disease with rFVIIa use. In this meta-analysis and systematic review, the authors summarize the evidence regarding the effects of PCC and rFVIIa on chest tube output, incidence of adverse events, and mortality of adult patients undergoing cardiac surgery. A total of 962 patients from seven retrospective observational studies were included in the pooled analysis. There was a significant reduction in the primary outcome: total chest tube output (mean difference: –301.01 mL, 95% confidence interval [CI] –550.54 to –51.48). PCC was associated with a significant reduction in total thromboembolic disease (odds ratio: 0.55, 95% CI 0.34 to 0.89), deep vein thrombosis (odds ratio 0.28, 95% CI 0.15 to 0.52), and cryoprecipitate transfusion (mean difference: –3.93, 95% CI –7.64 to –0.21). There were no significant differences between groups in the incidence of AKI or mortality. Five studies were deemed at moderate risk of bias, and two at serious risk. PCC has been shown to have a beneficial effect on reducing chest tube output and incidence of thromboembolic disease, with no increase in AKI compared with rFVIIa.