INTRODUCTION: Blood loss in Total Joint Arthroplasty can be significant and often under-estimated. This study aims to investigate the safety and efficacy of different routes of tranexamic acid (TXA) administration in reducing blood transfusion after Total Hip Arthroplasty (THA) and Total Knee Arthroplasty (TKA). The secondary aim is to find the safest and most efficacious route and dose of TXA. MATERIAL AND METHODS: PubMed, Embase, Cochrane library, China National Knowledge Infrastructure, and OpenGrey were systemically searched for randomised controlled trials investigating the efficacy and/or safety of TXA for THA and/or TKA. Network meta-analysis, comparing the number of transfusion and deep vein thrombosis (DVT) among different interventions, was performed using a multivariate meta-regression model with random-effects, adopting a frequentist approach. RESULTS: 211 publications (20,639 individuals) were included. For outcome of transfusion, all interventions showed significantly lower transfusion rates compared to placebo. When compared to placebo, TXA via intra-venous and topical showed statistically significant lowest risk ratio (RR = 0.11, 95CI: 0.03, 0.41). For safety, TXA via topical showed relatively lowest risk ratio (RR = 0.75, 95CI 0.44, 1.30). TXA via topical and intra-articular had the highest but statistically insignificant RR (RR = 1.10, 95%CI: 0.51, 2.38). Therefore, current studies did not reveal any significant safety issue in using TXA. CONCLUSION: All forms of TXA administration showed significantly lower transfusion rate compared to control. There is a trend towards better efficacy with intra-venous and topical. In patients with higher risk of thrombosis, physicians may consider topical alone for its best safety profile.