83 patients undergoing bilateral simultaneous total knee arthroplasty were included in this randomized trial to evaluate the comparative efficacy of three different methods of tranexamic acid (TXA) administration. Patients were randomized to receive one pre-operative and two intra-operative intravenous dosages, two intra-operative intravenous dosages, or two intraoperative local applications of TXA. Total blood loss and drain blood loss were evaluated over the first two postoperative days. Patients in the pre-operative and two intra-operative dose group had a significantly lower postoperative drain blood loss on the first day after surgery when compared to the other two groups. Postoperative blood drainage on the second postoperative day did not significantly differ between the three groups, nor did total blood loss based on hemoglobin drop from preoperatively to 5 days postoperatively.