OBJECTIVE: The purpose of this study was to determine the efficacy and safety of combined intravenous and topical use of tranexamic acid (TXA) in patients undergoing separation surgery for thoracolumbar spinal metastases by evaluating perioperative blood loss and complications. METHODS: A total of 54 patients with thoracolumbar spinal metastases who received separation surgery in our hospital from 2021 to 2024 were retrospectively analyzed and divided into 3 groups according to the use of TXA. Combined use of TXA group (group A) included 20 patients, intravenous TXA group (group B) contained 18 patients, and 16 cases received no TXA. The evaluation indexes included perioperative blood loss, hematologic parameters, surgical time, drain days, perioperative transfusions, and the presence of complications. RESULTS: During separation surgery for thoracolumbar spine metastasis, TXA decreased the perioperative blood loss significantly (P< 0.001). Compared with TXA infusion alone, combined usage of TXA reduced postoperative blood loss significantly (P< 0.001). Number of drain days was 4.00 +/- 1.55, 5.50 +/- 1.56 and 8.50 +/- 2.81, respectively, which TXA showed conspicuous effect on intraoperative transfusion rate. No complications happened except for 1 patient who experienced respiratory aspiration in group B. CONCLUSIONS: The application of TXA in separation surgery of spinal metastases can obviously reduce drain days, perioperative blood loss, an dintraoperative transfusion rate. The combination of intravenous infusion and topical use of TXA is more effective than intravenous use alone, which showed a strong synergistic effect; additionally, it does not increase the risk of venous thromboembolism and wound infection.