To study the Adverse drug reactions (ADRs) experienced by MDR TB patients put on DOTS plus regimen. The longitudinal cohort study was conducted by following a cohort of 142 MDR TB patients registered for DOTS plus therapy in 2010 under Revised National Tuberculosis Control Programme (RNTCP). Two follow ups were taken in a cohort of 142 MDR TB patients, first at completion of 6 months of treatment and second after completion of 24 months of treatment. Subjects were interviewed to study side effects of DOTS plus regimen. After 6 months of treatment, 48.59%(69) patients developed ADRs and between 6 months and 24 months of treatment 54.93%(78) patients developed ADRs out of total 142 at both the milestones. GI disturbances were 54.9% at 1st follow up and 46.54% at second follow up. Other side effects like headache, arthralgias, decreased hearing and skin reactions were also reported in varying frequencies. Average duration of ADRs was 60-90 days at both the follow ups. 62.68% of all ADRs were managed by symptomatic treatment and dose reduction was done in 4.47% of the patients in 2nd follow up. ADRs were experienced by more than half of the patients in the study and they increased as the duration of treatment increased. GI disturbances, Headache and Arthalgia were most common ADRs among patients. Most of them were managed by symptomatic treatment.