376 patients scheduled for total knee arthroplasty were randomized to one of four different tranexamic acid administration protocols. Patients received either intravenous administration only, intraarticular administration only, combined intravenous/low-dose intraarticular administration, or combined intravenous/high-dose intraarticular administration. The total blood loss, the incidence of transfusion, and the incidence of thromboembolic complications were compared between groups. Analysis of variance (ANOVA) testing demonstrated significant differences between the four groups in total blood loss, which was lowest in the combined IV+high-dose IA TXA group, higher and similar in the IV+low-dose IA TXA and IA TXA alone groups, and highest in the IV TXA alone group. No transfusion was necessary for any participant of any group.