OBJECTIVE different strategies have been developed to reduce blood loss in total knee arthroplasty (TKA). The efficacy of both systemic and local tranexamic acid (TXA) administration is demonstrated in the literature. The aim of the present study was to compare the efficacy of systemic, local and combined (systemic + local) administration of TXA in reducing blood loss after TKA. METHODS we enrolled all patients submitted to a primary TKA in our department between November 2014 and August 2015. They were divided into three groups corresponding to the method of TXA administration used: intravenous (IV), intra-articular (IA), and a combination of the two. Demographic data, as well as preoperative hemoglobin and platelet levels, were collected. The primary outcome was the maximum hemoglobin loss, while the secondary outcomes were the amount of blood in the drain (cc/hour) and the rate of transfusions; postoperative pain was also assessed. Student's t-test or a χ2 test was used to evaluate between-group differences, using p<0.05 as the cut-off for statistically significant differences. RESULTS the sample comprised 34 patients: IV, 10 cases; IA, 15 cases, and combined (IV + IA), 9 cases. The average age of the patients was 71.1±6.4 years. No significant differences in the outcome measures were found between the groups, with the exception of a significantly lower maximum hemoglobin loss in the combined versus the IV group (p=0.02). There were no differences between the groups in the amount of blood in the drain or the rate of transfusions. CONCLUSIONS the data from this preliminary study, as well as data from the literature, confirm that TXA administration is safe and effective in reducing total blood loss in TKA, and no administration protocol seems to be superior to the others. METHODS Level II, prospective comparative study.