Objectives: The study aimed to explore the efficacy and safety of linezolid-based chemotherapeutic regimens for patients with postoperative multidrug-resistant spinal tuberculosis. Methods: The randomized controlled study included 50 Mycobacterium tuberculosis culture or pathological-confirmed multidrug resistant tuberculosis patients who received spinal surgery from January 2018 to February 2020. Twenty-five patients were assigned to the control group and the study group, respectively. Random number method was used for patient allocation and they were treated with levofloxacin, pyrazinamide, thioisonicotinamide enteric-coated tablet, amikacin sulfate injection, and sodium p-amino salicylate injection, accompanied by linezolid or not. Results: The overall effective rate of the study group was higher than that of the control group (88.00% vs 64.00%, P