Purpose: The 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 2-level lumbar fusion surgery. Methods: 280 patients scheduled for 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. Results: The TBL was 635.49 ± 143.60, 892.62 ± 166.85, 901.11 ± 186.25, and 1,225.11 ± 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 was reported by 1, 2, and 2 patients in the combined group, topical group, and control group, respectively, there is no intergroup difference. Conclusions: The combined use of TXA effectively reduced total blood loss and blood transfusion rate in patients aged over 60 scheduled for 2-level lumbar fusion, without increasing the incidence of DVT and PE formation.