Objective: A systematic review of randomized controlled trials (RCTs) and non-RCTs was performed to evaluate the efficacy and safety of reducing blood loss using fibrin glue and tranexamic acid in patients who underwent total knee arthroplasty (TKA). Method: Relevant randomized controlled trial (RCTs) and non-RCT literature dealing with fibrin glue and tranexamic acid in TKA for reducing total blood loss was collected and searched from Medline, Embase, Pubmed, and the Cochrane Library for publication dates up to September 2015. After testing for publication bias and heterogeneity across studies, data were aggregated for random-effects modeling when necessary. Results: Three RCTs and two non-RCTs were eligible for data extraction and thus were included for meta-analysis. Compared with fibrin sealant, intravenous tranexamic acid may be more effective in reducing the need for transfusion (RR 2.62, 95% CI 1.64 to 4.18, P<0.0001). There was no significant difference in the total blood loss (MD=273.30, 95% CI -129.70.70 to 672.30, P<0.00001), hemoglobin values (SMD -0.74, 95% CI -1.08 to -0.40, P<0.00001), thromboembolic events (RR 4.00, 95% CI 0.46 to 35.15), fever (RR 0.63, 95% CI 0.21 to 1.85), hematoma (RR 1.03, 95% CI 0.28 to 3.70) or infection (RR 0.46, 95% CI 0.11 to 2.03) when comparing the fibrin glue group and the tranexamic acid group. Conclusions: The current meta-analysis indicated that tranexamic acid could be more effective in reducing the number of patients who need transfusions and can comparatively improve hemoglobin values. The fibrin glue and tranexamic acid groups had no distinction with respect to the incidence of thrombolism events. Furthermore, tranexamic acid is more economical than fibrin glue.