Background: Dexmedetomidine has shown potential in pain control in patients undergoing Total Knee Arthroplasty (TKA). However, the combination of nerve block and dexmedetomidine may be a preferred alternative for postoperative analgesia after TKA. The aim of this study was to perform a meta-analysis on existing randomized controlled trials (RCTs) to determine the efficacy and safety of dexmedetomidine as an adjunct to local anesthetics in nerve block after TKA.Methods: A literature survey was conducted in the databases of PubMed, Embase, Cochrane Library, Web of science and ScienceDirect for the RCTs completed before February 1st, 2020 that met pre-specified inclusion criteria. The primary outcomes included the pain scores, duration of analgesia, opioid consumption within 24 hours postoperatively, and the level of patient satisfaction. The secondary outcomes included the motor strength, degree of sedation, postoperative nausea and vomiting, and other related complications. The methodological quality was assessed by the Cochrane risk of bias tool. Results: The initial literature search yielded 143 studies, out of which seven studies met the inclusion criteria. The pooled data indicated that dexmedetomidine combined with local anesthetics in nerve block in TKA decreased the postoperative pain scores at rest as well as at motion (SMD=-1.01[95%CI, -1.29 to -0.72], p<0.01; SMD=-1.01[-1.25 to -0.77], p<0.01) respectively, decreased the total opioid consumption within 24 hours(SMD=-0.63[-0.86 to -0.40],p<0.01), prolonged the duration of analgesia (SMD = 0.90 [0.64 to 1.17], p < 0.01), improved motor strength (SMD = 0.23 [0.01 to 0.45], p = 0.04), improved the degree of sedation (SMD = 0.94 [0.70 to 1.18], p < 0.01), and increased the level of patient satisfaction (SMD = 0.88 [0.60 to 1.17], p < 0.01) without increasing nausea and vomiting (RD = -0.05 [-0.11 to 0.01], p = 0.14), as well as other complications (RD = -0.01 [-0.08 to 0.07], p=0.89), compared with local anesthetics alone.Conclusions: It is effective and safe for dexmedetomidine as an adjunct to local anesthetics in nerve block in TKA to relieve postoperative pain, decrease total opioid consumption, prolong analgesic duration and increase patient satisfaction without increasing related complications. Based on the quality of evidence, this meta-analysis recommends that dexmedetomidine can be used in a regular treatment regimen and as an adjunct addition to local anesthetics in nerve block for patients undergoing TKA.Registration: This meta-analysis was prospectively registered on PROSPERO (International prospective register of systematic reviews) and the registering number was CRD42020169171.