Total knee arthroplasty (TKA) has been proven to be a successful surgical procedure to correct deformity, relieve pain, and restore knee function. However, about 10 to 38% of patients following TKA require blood transfusion ranging between 1,000 mL and 2,000 mL for massive postoperative blood loss. [1,2] Blood transfusion may lead to transfusion-related complications and increase the medical burden. [3,4] Tranexamic acid (TXA), a synthetic lysine analogue, can competitively inhibit the activation of plasmin binding protein and plasminogen has been commonly utilized to reduce blood loss during TKA. [5,6] Multiple studies have reported that the intravenous (IV), Objectives: In this meta-analysis, we aimed to compare the efficacy and safety of peri-articular injection (PAI) and intraarticular injection (IAI) of tranexamic acid (TXA) in total knee arthroplasty (TKA). Patients and methods:We performed a comprehensive literature search from electronic databases such as Springer, Web of Science, PubMed, Cochrane Library databases, and ScienceDirect up to October 2021. The language of identified articles was not restricted. The keywords used for the search strategy included: "tranexamic acid", "total knee arthroplasty", "peri-articular injection" and "intra-articular injection".Results: Two randomized-controlled trials (RCTs) and four non-RCTs with a total of 491 patients met the inclusion criteria. Of the patients, 242 patients were in the PAI group and 249 patients were in the IAI group. No significant difference was observed between the two groups in hemoglobin drop, postoperative drainage volume, total blood loss, blood transfusion requirements, or units of blood transfused. There was no significant difference between the two groups regarding postoperative infection or deep venous thrombosis. Conclusion:The PAI of TXA is comparable to IAI of TXA in decreasing postoperative blood loss during TKA.