In our cohort, 711 received EACA, 445 received TXA, and 643 (control group) received no antifibrinolytic. Both antifibrinolytic groups had significantly fewer patients receiving red blood cell (RBC) transfusions when compared with control group (EACA 6.8% [P < .0001], TXA 9.7% [P < .0001] vs control group 24.7%). Average number of RBC units per patient were similar for EACA and TXA (0.11 units/patient and 0.15 units/patient, respectively), and both were significantly lower than the control group (0.48 units/patient, P < .0001). No significant difference was noted in mean RBC units per patient and percentage of patients transfused between EACA and TXA groups (P = .144, P = .074). Logistic regression showed no difference between EACA and TXA when adjusting for age, gender, higher severity of illness levels, admission hemoglobin, performing surgeon, and hospital. Medication acquisition cost for EACA averaged $2.70 per surgery compared with TXA at $39.58 per surgery.