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Prospective cohort study.We report the first study of multidrug-resistant tuberculosis (MDR-TB) in the spine. The aim was to determine the clinical, radiologic, and drug resistance profile as well as the factors associated with treatment outcome of MDR-TB in the spine.Tuberculosis of the spine is the most common extrapulmonary form of tuberculosis in the Asian subcontinent. The disease in few cases is resistant to the primary anti-Koch's medications and the number of cases detected is on the rise. Multidrug resistant form of tuberculosis of the spine is ill reported in the literature. The diagnosis, management thus remains a challenge to the treating surgeon. This study tries to assess these critical issues of this “new” disease.Described here are the clinical characteristics of 25 MDR-TB spine patients identified in the study and their drug susceptibility patterns. They were followed up clinically, radiologically after a biopsy, culture, and Drug Susceptibility Testing. According to their Drug Susceptibility Testing pattern and previous history of Anti-Tubercular Treatment (ATT), individualized treatment regimens were tailored for each patient by an expert physician.Majority of the patients seen in the present study were in the productive years of their life. (Males (9) mean age: 38.5 years and females (16) mean age: 34.3 years. Four patients were defaulters of the ATT. The average number of drugs used was 6, including 4 second line drugs. Average treatment duration was 24 months. Almost 50% of the patients had adverse drug effects. Of the 25 patients, 19 achieved healed status and 6 are still on treatment. Four patients required surgery for mechanical instability of the spine. Radiologic improvement was observed in all the cases after a mean treatment of 6 months. Five predictors were identified for successful outcome of MDR-TB. They include progressive clinical improvement at 6 months, radiologic improvement during treatment and disease with Mycobacterium tuberculosis strains exhibiting resistance to less than or up to 3 antitubercular drugs, use of less than or up to 4 second-line drugs in treatment, and no change of regimen during treatment.MDR-TB of the spine is a different disease and is here to stay. There is an urgent need to include culture and drug susceptibility testing in the protocol for the treatment of tuberculosis of the spine.