Objective: Drug resistant Mycobacterium tuberculosis is a public health threat globally. We described the drug resistance pattern of M. tuberculosis to first line anti-TB drugs and the prevalence of Multidrug resistant TB among TB patients at tertiary hospital Nnewi, Nigeria.Methods: Sputum specimens from 550 suspected TB patients were analyzed for AFB. The smear positive samples were subjected to culture and drug susceptibility testing to first line anti-TB drugs on Lowenstein-Jensen medium.Result: Out of 180 (32.7%) culture positive samples subjected to DST, 97 (53.8%) were susceptible to all first line anti-TB drugs while 83 (46.1%) were resistant to one or two anti-TB drugs. The level of resistance was significant at p<0.05 identifying three patterns, Mono-drug resistance in 34(18.8%) patients, Multi-drug resistance in 14 (7.7%) and Poly drug resistance in 35 (19.4%) patients. The proportion of TB cases with resistance to single drugs ranged from 5 (2.7%) for rifampicin to 12 (6.6%) for isoniazid and previously treated TB 8 (4.4%) patients was a significant factor (P<0.000) to development of MDR-TB compared to new TB patients 6(3.3%) within the age range of 21-40 years. Other factors such as age, gender and HIV positive status were not significantly associated with the development of any resistance. Conclusion:The investigation highlights the presence of drug resistant TB with high prevalence of MDR-TB in the studied community. Larger studies are urgently recommended to improve TB clinical management and control efforts.