PurposeThe current study was conducted to assess the efficacy and safety of the intravenous (IV) administration combined with topical administration of tranexamic acid (TXA)in patients (aged over 60) scheduled for a 2-level lumbar fusion surgery.MethodsTwo hundred eighty patients scheduled for a 2-level lumbar fusion surgery were randomized into four groups, including an IV group, a local group, a combined group, and a control group. Patients in the combined group, in the IV group, in the topical group, and in the control group were administrated with 15 mg/kg of IV-TXA + 2 g TXA in local, 15 mg/kg IV-TXA, 2 g TXA in local, and 100 ml IV, respectively. The results of total blood loss (TBL), maximum hemoglobin drop, the transfusion rate, and the number of allogeneic blood units were compared. Deep venous thrombosis (DVT) and pulmonary embolism (PE) events were monitored and recorded.ResultsThe TBL was 635.49 ± 143.60, 892.62 ± 166.85, 901.11 ± 186.25, and 1225.11 ± 186.25 mL for the combined group, the IV group, the topical group, and the control group, respectively (p = 0.015, p = 0.001, respectively). The average maximum hemoglobin drop in the four above groups was 2.18 ± 0.24, 2.80 ± 0.37, 2.40 ± 0.64, and 3.40 ± 1.32 g/dL, respectively. No PE event was reported during the follow-up. Although asymptomatic DVT events were reported by 1, 2, and 2 patients in the combined group, topical group, and control group, respectively, there is no intergroup difference.ConclusionsThe combined use of TXA effectively reduced the total blood loss and blood transfusion rate in patients aged over 60 scheduled for a 2-level lumbar fusion, without increasing the incidence of DVT and PE formation.