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TB treatment course is at least a 6-month of a combination of first line drugs. The increasing frequency of anti-TB drug resistance has been a major setback. It is necessary that we prevent further development of the resistance strains and optimize the available first line drugs or TB will become once again incurable. Isoniazid continues to have a prominent role in treatment regimens for TB disease and Latent TB Infection.It is essential to understand what factors may be contributing to its resistance so that clinicians can make informed treatment decisions when evaluating the patients. This work aimed to identify the prevalence and factors associated with TB drugs resistance among the new tuberculosis patients in Kampala-Uganda.