Only a few of studies have reported whether Tranexamic acid (TXA) has the same benefits during total ankle replacement as hip and knee replacements. In our study, we hypothesized that TXA was effective in reducing the perioperative blood loss without increasing the risk of symptomatic venous thromboembolism of patients during total ankle replacement. We retrospectively reviewed 71 patients who underwent total ankle replacement at the foot and ankle surgery center of our institution between January 2017 and May 2021. Patients were divided into two groups according to whether they received intravenous tranexamic acid or not. Patients who received intravenous TXA showed significantly lower estimated intraoperative blood loss, hidden blood loss and total blood loss. The early AOFAS score and ROM at the first month follow up of TXA group were better than the NO-TXA group and the incidence of early wound infection and poor healing (< 1 month postoperative) was significant lower than NO-TXA group. Use of TXA was not associated with significant changes in the incidence of postoperative symptomatic venous thromboembolism. We conclude that intravenous TXA can safely and effectively reduce perioperative blood loss and the incidence of early wound infection and poor healing in total ankle replacement, without increasing the risk of symptomatic venous thromboembolism.The application of TXA following total ankle replacement helped improve ankle function and patient quality of life during the early stage.