Background <p>Tranexamic acid (TXA) is considered a potential therapeutic approach to mitigate postoperative inflammatory responses; however, its anti-inflammatory effects remain controversial. This study conducts a systematic review and meta-analysis of randomized controlled trials aiming to investigate the efficacy of multi-dose TXA in exerting anti-inflammatory effects in hip and knee arthroplasty.</p> Methods <p>We identified potential relevant literature evaluating the anti-inflammatory effects of TXA in patients undergoing hip and knee arthroplasty from PubMed, Embase, and the Cochrane Library. Meta-analysis was performed using RevMan 5.3.</p> Results <p>Nine randomized controlled studies met the inclusion criteria. Meta-analysis results indicated that, compared with lower doses of TXA, multi-dose TXA significantly reduced the inflammatory markers IL-6 and CRP in patients undergoing hip and knee arthroplasty and shortened the length of hospital stay, with statistically significant results. Nonsignificant differences were found in the incidence of thromboembolic events.</p> Conclusion <p>Based on the current evidence, our results indicate that multi-dose TXA effectively reduces postoperative inflammatory responses in patients undergoing hip and knee arthroplasty. This anti-inflammatory effect is dose-dependent and is accompanied by a reduction in the length of hospital stay. Nonetheless, further high-quality, multicenter, large-sample-size randomized controlled trials are needed to confirm the anti-inflammatory effects of TXA.</p>