OBJECTIVE: To investigate whether intravenous combined with topical administration of tranexamic acid (TXA) is superior to intravenous administration alone in terms of blood loss, incision complications, functional recovery, and pain relief in high tibial osteotomy (HTO). METHODS: Clinical data of patients with knee osteoarthritis (OA) treated with unilateral HTO were retrospectively reviewed. The patients were grouped according to the TXA administration method, with 24 patients in the combined group and 21 in the solo group. In the combined group, 100 mL saline containing 1 g TXA was intravenously administered before application of a tourniquet, and 20 mL saline containing 2 g TXA was injected through a drainage tube after closure of the incision. Alternatively, 100 mL of saline containing 1 g TXA was intravenously administered before application of a tourniquet in the solo group. The blood loss and adverse events were compared between the two groups. RESULTS: All patients were followed for more than half a year. The drainage volume on the first day and total blood loss on the second day after surgery in the combined and single treatment groups were 130.06 ± 29.22 and 165.35 ± 43.08 mL (P < 0.05), respectively, and 327.17 ± 64.26 and 385.45 ± 63.31 mL (P < 0.05). There were no blood transfusions in either group. One case of delayed incision healing was observed in the solo group, and no such event occurred in the combined group. There were no significant differences between the two groups in terms of the following factors: the activated partial thromboplastin time (APTT) and prothrombin time (PT); levels of fibrinogen (FIB) and D-dimer on the second day after surgery; numbers of hospitalization days and thromboembolism events; and knee joint function and visual analog score 6 months after surgery. CONCLUSION: Intravenous combined with topical TXA administration in HTO is superior to intravenous administration alone for reducing postoperative blood loss and drainage volume without thromboembolic complications. However, even with only intravenous TXA administration, no cases of blood transfusion and only 1 case of incision complication occurred. At the same time, the combined use of TXA did not improve the recovery of knee joint function and pain relief after HTO.