Pain management after total knee arthroplasty (TKA) remains among the most important challenges for patients with TKA. Intra-articular local anesthetic has been shown to reduce postoperative pain following TKA. However, studies report conflicting results. This meta-analysis evaluated the efficacy and safety of single-dose intra-articular local anesthetics for pain control after TKA. Databases (Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, and Chinese Biomedical Databases) were searched to identify randomized, controlled trials comparing local anesthetic with placebo in patients undergoing TKA. Data were extracted independently by 2 researchers using a standardized form. Risk of bias was assessed with the use of the Cochrane Collaboration's tool for assessing the risk of bias by 2 observers. Relative risk, standardized mean difference, and corresponding 95% confidence interval were calculated. Seventeen trials met the inclusion criteria, for a total of 1338 participants. The results showed that, compared with the placebo group, the single local anesthetic group had a significant lower pain score with rest at 4, 8, 24, and 48 hours; less opioid consumption at 24, 48, and 72 hours postoperatively; and greater range of motion at 24, 48, and 72 hours. There were no significant differences between the 2 groups in length of hospital stay, nausea and vomiting, pruritus, sedation, or deep venous thrombosis. The study findings showed that pain relief after TKA was significantly better with intra-articular local anesthetic than with placebo.