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Background: Local infiltration anesthesia (LIA) and femoral nerve block (FNB) are commonly used analgesia methods after total knee arthroplasty (TKA). However, there is no definitive conclusion about which of these two analgesia modes is superior. Therefore, this study aimed to systematically evaluate the analgesic effects of LIA and FNB after TKA., Methods: We used the terms "total knee replacement, knee replacement, total knee arthroplasty, knee arthroplasty, local infiltration analgesia, periarticular infiltration, periarticular injection, intra-articular infiltration, intra-articular injection, peripheral nerve block, femoral nerve block" to search the PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu databases. The search period was set from the date of establishment of the database to September 2021. The Cochrane risk of bias tool was used to evaluate the quality of the included studies, and network meta-analysis was performed using Stata14.0 and RevMan 5.30 software., Results: Nine articles were included for analysis. The results of meta-analysis showed that compared with LIA and FNB, the difference in opioid use [mean difference (MD) -4.35, 95% confidence interval (CI): -7.26 to -1.45] was statistically significant. However, there was no significant difference between the static visual analogue score at 24 hours postoperatively (MD 0.20, 95% CI: -0.91 to 1.31), the visual analogue score for exercise visual analogy at 24 hours after surgery (MD 0.10, 95% CI: -0.12 to 0.32), and the length of hospital stay (MD 0.05, 95% CI: -0.40 to 0.50)., Discussion: LIA and FNB have similar effects on pain relief after TKA, but LIA can reduce the use of analgesic drugs and is easy to operate. Therefore, LIA can be used as the priority analgesic method for patients with TKA. However, multi-center, large-sample, high-quality, randomized controlled trials are still needed for further verification., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-286/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)