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We conducted the present meta-analysis to assess the efficacy and safety of tranexamic acid (TXA) plus diluted-epinephrine (DEP) for patients with total joint arthroplasty (TJA, including total knee arthroplasty (TKA) and total hip arthroplasty (THA)).Electronic databases (PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Wanfang databases, and Google databases) were systematically searched up to December 2016. Only randomized controlled trials (RCTs) were included. The primary outcomes were total blood loss and need for transfusion. The secondary outcomes were hemoglobin drop and the incidence of deep venous thrombosis (DVT) and hematoma. Continuous outcomes and discontinuous outcomes were compiled as the weighted mean difference (WMD) and relative risk (RR) with 95% confidence intervals (CI), respectively.A total of 5 RCTs with a total of 493 patients were eligible and ultimately included in the meta-analysis. Compared with the TXA group, TXA plus DEP yielded a significant reduction in total blood loss (WMD = –244.78; 95% CI –290.12 to –199.44; P < .001), need for transfusion (RR = 0.27; 95% CI 0.15–0.48; P < .001) and hemoglobin drop (WMD = –0.81; 95% CI –1.22 to –0.40; P < .001). There was no significant difference in incidence of DVT (RR=0.67; 95% CI 0.27–1.64; P = .382) or hematoma (RR=0.89; 95% CI 0.30–2.61; P = .831) between the TXA plus DEP group and the TXA group.TXA plus DEP can decrease perioperative blood loss without increasing the incidence of DVT compared with TXA alone. However, considering the limited number of included RCTs, this conclusion should be interpreted cautiously, and more high-quality RCTs are needed to verify the efficacy and safety of TXA plus DEP for TJA patients.