Aims: The combined (IV (intravenous) þ topical) use of tranexamic acid (TXA) has been shown to be a safe method and more effective than single (IV or topical) application. The optimal administration method of TXA is still being investigated and safety, efficiency and cost are the three main crucial parameters in achieving the best administration method. We aimed to determine whether combined (oral þ topical) use of TXA reduced blood loss and transfusion rates more than single (topical) administration in TKA and whether oral þ topical use is as safe and efficient as the IV þ topical use, in addition to the main advantage of relatively low cost. Methods: In this prospective, randomized study, 100 patients were randomly assigned to either the topical TXA group or the combined (oral þ topical) TXA group. There were no significant differences between the groups in age, body mass index or gender. The haemoglobin and haematocrit levels of each patient were recorded preoperatively and on post-operative days 0, 1, 2 and 3. The post-operative suction drainage and blood transfusion volumes were also recorded. Results: There were statistically significant differences between the groups in haemoglobin and haematocrit levels on post-operative days 0, 1, 2 and 3 (p < 0.05) in favour of the combined group. The post-operative drainage amounts (p ¼ 0.0001), measured blood loss volume (p ¼ 0.003) and transfusion rates (p ¼ 0.03) were lower in the combined (oral þ topical) group compared to the topical group. Conclusions: Of the different methods of TXA administration, the combined use of oral and topical TXA is a safe, efficient and low-cost method in reducing blood loss and transfusion rates after TKA.