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Total knee arthroplasty is associated with substantial blood loss and the risks of transfusion. Conflicting reports have been published regarding the effectiveness and safety of tranexamic acid in reducing postoperative blood loss in total knee arthroplasty. We performed a meta-analysis to investigate the effectiveness and safety of tranexamic acid in reducing postoperative blood loss in total knee arthroplasty.A meta-analysis was performed to assess the effectiveness and safety of using tranexamic acid in total knee arthroplasty. Randomized controlled trials that had been published before May 2011 were retrieved, and fifteen studies met the inclusion criteria. The weighted mean difference in blood loss, number of transfusions per patient, prothrombin time, and postoperative activated partial thromboplastin time and the summary odds ratio of transfusion, deep-vein thrombosis, and pulmonary embolism were calculated in the group of patients who received tranexamic acid and the group of patients who received a placebo.The amount of blood loss and the number of blood transfusions per patient were significantly less and the proportion of patients who required a blood transfusion was smaller in the tranexamic acid group compared with the placebo group. No significant difference in prothrombin time, activated partial thromboplastin time, deep-vein thrombosis, and pulmonary embolism was detected between the tranexamic acid group and the placebo group.The meta-analysis shows that the use of tranexamic acid for patients undergoing total knee arthroplasty is effective and safe for the reduction of blood loss.Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.