During liver transplantation (LT), profound activation of the fibrinolytic system can contribute significantly to perioperative bleeding. Prophylactic administration of antifibrinolytic agents has been shown to reduce blood loss and the need for allogeneic transfusion in these conditions. This prospective randomized trial included 51 cirrhotic patients undergoing LT. Patients were randomly assigned to receive either 280 mg of aprotinin (AP) followed by 70 mg per hour or 40 mg per kg tranexamic acid (TA) followed by 40 mg per kg per hour, administered from the end of the anhepatic phase until 2 hours after reperfusion of the graft, and the effects on blood loss and red blood cell (RBC) transfusion requirements were compared. Transfusion policy was standardized in all patients. In addition, the biological effects of the two drugs, as assessed by coagulation and fibrinolytic markers obtained during surgery, were evaluated in a subgroup of patients from each treatment group and compared with an historical control group that did not receive antifibrinolytic drugs. There was no significant difference between the two groups in perioperative blood losses (AP, 6200 [4620-8735] mL; TA, 5945 [4495-8527] mL; median [range]) or in RBC transfusions requirements (AP, 9 [6.75-15.25] units; TA, 10 [6.5-13.5] units). Inhibition of fibrinolysis was observed with both drugs compared with the control group. Coagulation appeared to be activated more with AP, however, whereas fibrinolysis was inhibited more by TA. Blood losses and RBC transfusion requirements were comparable regardless of the drug administered. TA may be as valuable as AP for controlling fibrinolysis in LT.