The administration of tranexamic acid (TA) prior to cardiopulmonary bypass (CPB) has been associated with reduced bleeding during and after cardiac surgery. In a prospective, randomized, controlled, double-blind clinical trial, adult patients undergoing repeat open heart surgery received TA (n = 17) or an equal volume of saline placebo (n = 13). In the TA group, a 20-mg/kg intravenous (IV) initial dose of TA at akin incision was followed by an infusion of 2 mg.kg-1.h-1, which continued for the duration of the surgical procedure. Identical transfusion guidelines were followed in both groups. Routine coagulation tests, D-dimer levels, mediastinal tube drainage, and transfusion requirements were compared. Cumulative postoperative mediastinal tube drainage measured at 24 h was 649 +/- 391 mliter (mean +/- SD) in the TA group compared with 923 +/- 496 mliter in the placebo group (P < 0.01). Forty-eight-and 72-h mediastinal tube drainage were also significantly less in the TA group (P < 0.01). Seven of 17 TA patients received to transfusion of allogeneic blood products compared with 1 of 13 placebo patients (P = 0.047). The incidence and volumes of platelet and fresh frozen plasma transfusion in the TA group were not significantly different in comparison with the placebo group. The perioperative increase in D-dimer levels (post-CPB minus pre-CPB) in the placebo group (median difference = 675 ng/mliter, range 125-1648) was significantly more than in the TA group (median difference = 182 ng/mliter, range -426-1950; P = 0.003). Sternal closure occurred in 41 +/- 21 min in the TA group and 61 +/- 49 min in the placebo group (P = 0.14), and the subjective bleeding score was less in the TA group than in the placebo group (2.38 +/- 0.78 vs 3.08 +/- 1.04; P = 0.045). The data from the current study support the prophylactic use of TA in patients undergoing repeat cardiac surgery. TA administered prior to CPB reduced the incidence of allogeneic transfusions and postoperative mediastinal tube drainage, and improved the subjective assessment of post-CPB hemostasis in a group of patients at moderately high risk for perioperative bleeding.