BACKGROUND Tranexamic acid (TXA) administration is supported by numerous evidence in reducing blood loss after total knee arthroplasty (TKA). The combination of intravenous (IV) and intra-articular (IA) TXA administration revealed good result in blood loss reduction with less evidence of venous thromboembolism event (VTE). Several literature reviews portray that peri-articular (PA) administration yields similar hemostasis in comparison to IV route. However, there is no report on the clinical effect of combining PA + IA TXA in blood loss reduction and its complications, compared to combining IV + IA TXA after TKA. METHODS We conducted a double-blind, randomized controlled trial comparing the use of PA + IA TXA administration and IV + IA TXA administration in 70 patients who were scheduled for unilateral primary TKA. Thirty-five patients were assigned for PA + IA injection (Group 1) and anoter 35 patients were assigned for IV + IA injection (Group 2). Primary outcomes included total blood loss at 48 h, and the need for blood transfusion. Secondary outcomes included thigh and leg circumference, degree of knee flexion, and postoperative complications. RESULTS The calculated blood loss at 48 h showed no difference between Groups 1 and 2 (617 ml vs. 632 ml, p = 0.425). The total hemoglobin and hematocrit changes were not different (1.89 g/dL vs. 1.97 g/dL, p = 0.371 and 5.66% vs. 5.87%, p = 0.391). There was no need for blood transfusion in either group. However, lower thigh swelling was significant in Group 1 (2.15 cm vs. 2.79 cm, p = 0.04). Leg circumferences at 48 h was also lower in Group 1 (42.12 cm vs. 42.77 cm, p = 0.04). There was no significant difference in knee flexion decrease between the two groups (38° vs. 37°, p = 0.425). There were no VTE complications or infections found in either group. CONCLUSIONS Combined PA + IA TXA administration had similar efficacy in blood loss reduction and blood transfusion when compared to combined IV + IA TXA. The first group displayed less soft tissue swelling. The combination of PA + IA TXA administration can be used as an alternative regimen to avoid IV TXA administration.