Tranexamic acid (TXA) is one of the most common hemostatic drugs used in surgical patients and is known to help reduce blood loss volume. Here, researchers reviewed the literature comparing intravenous (IV) and topical TXA administration, as well as combined delivery. A total of 26 randomized, controlled trials were included in the analysis. Topical and IV patients did not have significant differences in total blood loss volume, drain blood loss, postoperative hemoglobin (Hb) levels, Hb decline, length of hospital stay, transfusion rate, and occurrence of venous thromboembolism (VTE). However, single-route patients had significantly increased total blood loss volume, greater Hb decline, and higher transfusion rates, but drain blood loss, postoperative Hb levels, and VTE events did not largely differ between the groups.