Tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) are antifibrinolytic agents commonly used to reduce blood loss in total knee arthroplasty (TKA). Although TXA is widely adopted, EACA offers a potentially more economical alternative. However, head-to-head comparisons using paired designs remain limited. The present randomized controlled trial included 294 patients undergoing bilateral TKA. Each patient received topical TXA in one knee and topical EACA in the contralateral knee in a randomized sequence. Primary outcomes included total perioperative blood loss and total drain output over 3 days. Secondary outcomes included transfusion requirement, postoperative complications, and cost-effectiveness. The statistical analyses included paired t-tests, linear mixed-effects models for effect modification, logistic regression for transfusion and complications, and cost-effectiveness analysis comparing drug costs against blood loss reduction. Data from 294 patients (588 knees) were analyzed. TXA was associated with a statistically significant but modest reduction in total blood loss compared with EACA (mean difference: 10.03 mL, p < 0.001), well below the predefined non-inferiority margin of 200 mL. Similarly, drain output was also found to be lower in TXA-treated knees (mean difference: 10.07 mL; p  =  0.0001), but the difference was not considered clinically significant. The rates of transfusion and postoperative complications were low (2.72 and 3.74% respectively). Cost-effectiveness analysis revealed EACA to be more cost effective as compared with TXA. Topical EACA was found to be non-inferior to TXA in reducing perioperative blood loss in TKA, with equivalent clinical outcomes and greater cost-effectiveness. These findings support the use of EACA as a cost-saving alternative to TXA, particularly in resource-limited settings.

Received: 15 August 2025

Accepted: 06 November 2025

Accepted Manuscript online:
12 November 2025

Article published online:
24 November 2025

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