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Perioperative blood loss is still an unsolved problem in total knee arthroplasty (TKA). The efficacy of the preoperative use of tranexamic acid (TXA) plus drain-clamping to reduce blood loss in TKA has been debated. This meta-analysis aimed to illustrate the efficacy of TXA plus drain-clamping to reduce blood loss in patients who underwent a TKA.In February 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, the Cochrane Database of Systematic Reviews, and Google Scholar. Data from patients prepared for TKA in studies that compared TXA plus drain-clamping versus TXA alone, drain-clamping alone, or controls were retrieved. The primary endpoint was the need for transfusion. The secondary outcomes were total blood loss, blood loss in drainage, the decrease in hemoglobin, and the occurrence of deep venous thrombosis. After testing for publication bias and heterogeneity between studies, data were aggregated for random-effects models when necessary.Ultimately, 5 clinical studies with 618 patients (TXA plus drain-clamping group = 249, control group = 130, TXA-alone group = 60, and drain-clamping group = 179) were included. TXA plus drain-clamping could decrease the need for transfusion, total blood loss, blood loss in drainage, and the decrease in hemoglobin than could the control group, the TXA-alone group, and the drain-clamping group (P < .05). There was no significant difference between the occurrence of deep venous thrombosis between the included groups (P > .05).TXA plus drain-clamping can achieve the maximum effects of hemostasis in patients prepared for primary TKA. Because the number and the quality of the included studies were limited, more high-quality randomized controlled trials are needed to identify the optimal dose of TXA and the clamping hours in patients prepared for TKA.