Tranexamic acid (TXA) is commonly used to reduce blood loss and blood transfusion in total knee arthroplasty (TKA). However, studies regarding the efficacy of intravenous TXA given during the intra-operative period are limited. To study the efficacy of intra-operative TXA regimen on reducing blood loss and blood transfusion in TKA. In this retrospective comparative study, 60 patients were divided into two groups. Patients in Group 1 were given 10 mg/kg intravenous TXA 10 minutes before inflation of the tourniquet and again immediately after deflation of the tourniquet. Patients in Group 2 did not receive TXA. Blood loss, blood transfusion, and complications were compared between the two groups. Study findings revealed that intra-operative TXA regimen could significantly reduce drained blood (660±117.8 ml vs. 1,141.7±157.9 ml, p<0.001), decreasing hemoglobin at 12 hours (1.8±0.3 g/dL vs. 2.5±0.5 g/dL, p<0.001) and blood transfusion (26.7% vs. 80.0%, p<0.001) with no increase in procedure-associated complications. Intra-operative TXA regimen has the efficacy on reducing blood loss and blood transfusion requirement in TKA without potential risk of complications.