Setting Tuberculosis (TB) still remains one of the major health problems facing humans. India accounts for almost a quarter of TB cases worldwide. The scenario is worsening owing to multidrug resistant-tuberculosis (MDR-TB). Assessment of local prevalence rates and detection of MDR-TB are important to rationalize therapy and prevent spread of resistant strains in community. Objective The study was undertaken to understand drug sensitivity patterns of tubercle bacillus and assess resistance trends in Meghalaya. Designs Specimens were screened for acid-fast bacilli, decontaminated by N-acetyl cysteine–sodium hydroxide method, and subsequently inoculated onto Lowenstein–Jensen media. Characteristic growth was biochemically identified as TB bacillus. Drug sensitivity assessment to first-line anti-TB drugs was performed by proportion method and sensitivity patterns noted. Results Among 103 specimens received, 23 showed acid-fast bacilli. Male to female ratio was 3 : 2. Fourteen (13.6%) pure isolates of Mycobacterium spp. were obtained. Biochemically 10 isolates were confirmed as M. tuberculosis. Drug sensitivity profile revealed highest mono resistance to isoniazid and streptomycin. Two (20%) isolates were MDR. Conclusion The study gives a brief overview of the menace of TB in Meghalaya. The study results provide valuable information about presence of primary MDR-TB and provide basis for future larger field surveys.