OBJECTIVES: With the introduction of newer molecular diagnostic tools to identify Mycobacterium tuberculosis , an increasing number of nontuberculous mycobacterium (NTM) is being identified. However, the drug resistance pattern of the NTM species identified is less explored. The objective of this study is to study the drug resistance patterns of Mycobacterium kansasii species isolated in a tuberculosis-endemic setting at South India. METHODS: A wide profile of NTM species were reported earlier from a prospective cohort of adults during 2017–2020. Out of this profile, a total of 22 M. kansasii species were subjected to drug susceptibility testing by two different methods: proportion sensitivity testing method and Sensititre testing method. RESULTS: Out of the 18 strains of M. kansasii subjected to Sensititre method of testing, the resistance pattern was demonstrated to be high for doxycycline (13) followed by rifampicin and trimethoprim/sulfamethoxazole (7). Out of the 22 strains subjected to proportion sensitivity testing method, 20 and 10 were resistant to isoniazid and ethambutol, respectively. CONCLUSION: There was a poor correlation between the treatment outcome and the resistance pattern of the antibiotics tested. With increasing numbers of NTM being reported, early and correct identification of NTM species is essential for the prompt initiation of appropriate treatment to achieve better outcome.