151 patients undergoing total knee arthroplasty were included in this randomized trial to evaluate the efficacy of different intravenous tranexamic acid administration protocols for reducing hidden blood loss. Patients were randomized into 3 groups: Group A (control) received intravenous (IV) TXA pre-op and IV placebo at 3 and 6 hours. Group B (3h TXA) received IV TXA pre-op and at 3 hours, and IV placebo at 6 hours. Group C (3h+6h TXA) received IV TXA pre-op, at 3 and at 6 hours, all patients received 1-g of topical TXA intraoperatively. The results of this trial indicated that the group that received additional TXA doses at 3 and 6 hours had a significant reduction in hidden blood loss, total blood loss, postoperative hemoglobin drop, and a shorter length of hospital stay when compared to the other two groups, without an increase in thromboembolic adverse events.