[Objective] To investigate the efficacy of multiple-dose intravenous tranexamic acid（TXA）on the control of perioperative bleeding in thoracolumbar burst fractures and enhanced recovery after surgery. [Methods] Consecutive patients with thoracolumbar single-segment burst fractures were prospectively randomized into groups that received 20 mg/kg body weight of TXA intravenously thirty minutes before the skin incision follwed by multiple-dose of 10 mg/kg at 3h, 6h and 12h after the surgery or normal saline protocol. Posterior decompression and reduction combined with short-segment internal fixation surgery was performed for all patients by using a consistent procedure. Intraoperative and postoperative blood loss as well as the total number of blood units transfused were compared between the two groups. Other variables such as the changes of hemoglobin and albumin levels, extubation time, and the occurrence of thrombotic diseases were recorded. [Results] Eighty-five patients were enrolled and randomized: 43 received TXA (experimental group) and 42 received placebo (control group). The intraoperative blood loss during the operation, amount of 48h postoperative drainage, blood transfusion rate, amount of blood transfusion, and extubation time were significantly lower in the experimental group than those in the control group. The hemoglobin concentration and albumin concentration in the control group were significantly lower than those in the experiment group 48h postoperatively. Compared with the experimental and the control group, intraoperative blood loss and 48h postoperative drainage volume were significantly reduced [(445.35 ± 146.42 VS 737.38 ± 286.77) ml; (279.30 ± 125.55 VS 480.38 ± 167.22) ml] (P <0.05). The transfusion rate in the control group was as high as 83.33%, while in the experiment group it was reduced to 41.86% (P<0.05). It is examined by color Doppler ultrasonography before discharge showed no deep vein thrombosis of the lower extremities in both groups, and showed no thrombus-related complications at the end of the follow-up of three months. [Conclusion] Multiple-dose perioperative intravenous TXA significantly reduce the perioperative blood loss, transfusion requirements, postoperative albumin loss and extubation time in patients with thoracolumbar burst fractures without the occurrence of thrombotic complications.