: The aim of this meta-analysis is to assess the effectiveness and safety of intravenous application tranexamic acid (TXA) in primary simultaneous bilateral total knee arthroplasty (TKA). We searched electronic databases including PubMed, Embase, the Web of Science, the Cochrane Library and the Google Scholar, for published studies involving the intravenous application TXA in primary simultaneous bilateral TKA. All randomized controlled trials were included. The focus of the meta-analysis was on the outcomes of total blood loss, drainage volume, transfusion requirements and deep venous thrombosis (DVT) and/or pulmonary embolism. The relevant data were analyzed using RevMan 5.2. Six high randomized controlled trials were included, with a total sample size of 394 patients. The intravenous application of TXA significantly reduced total blood loss [95% confidence interval (CI), -519.52 to -126.40; P = 0.001], drainage volume (95% CI, -551.76 to -138.57; P = 0.001) and transfusion requirements (risk ratio, 0.38; 95% CI, 0.21-0.68; P = 0.001) compared with the control group. In addition, there were no significant differences in the rate of DVT (P = 1.00) and/or pulmonary embolism between the two groups. Based on the current evidence, this meta-analysis showed that intravenous application of TXA is effective and a well tolerated treatment to reduce total blood loss, drainage volume and transfusion requirements without increasing the risk of DVT and/or pulmonary embolism in primary simultaneous bilateral TKA.