The purpose of this study was to compare the efficacy of intravenous and topical tranexamic acid (TXA) versus control group for reduction in blood loss following primary total knee arthroplasty (TKA). A total of 90 patients were prospectively allocated to each of three groups (control, intravenous IV and intra-articular) and underwent unilateral total knee arthroplasty. In the IV group, patients received one dose of TXA of 15 mg/kg before deflation of the tourniquet, while in the intra-articular group patients received 2 g TXA via the drain retrogradely after closure of the wound. The mean drained blood loss in control, IV and intra-articular groups was 415 ± 24, 192 ± 21 and 121 ± 17 ml, respectively. About 43 % (control), 23 % (IV) and 17 % (intra-articular) of each group required transfusion, and the mean transfusion was 338, 168 and 79 ml, respectively. Preoperative hemoglobin values decreased at 24 h by 2.80 ± 0.14, 2.24 ± 0.17 and 2.26 ± 0.18 mg/dl, respectively. TXA reduced blood loss and transfusion requirement. Compared with one-dose intravenous administration, intra-articular administration of TXA seems to be more effective in terms of reducing drained blood loss and transfusion frequency. We recommend administration of topical TXA in primary TKA in healthy patients to decrease perioperative blood loss.