INTRODUCTION: Pulmonary tuberculosis is respiratory infection caused by M.tuberculosis bacilli which occur via aerosol. First line drugs used in the treatment of TB are Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E). Use of multidrug regimens has been associated with increased incidence of adverse drug reactions, involving all the major organs. However the frequency of occurrence of ADRs to ATT involving major organs are not well known, so in this study we tried to find out the most commonly affected organ due to ATT. MATERIAL AND METHOD: This open, prospective, observational, non-comparative study was conducted from March 2015 to September 2016 in the Government Medical College, Amritsar. One hundred sputum positive patients of pulmonary tuberculosis on DOTS category I, of either sex, in the age group of 14 years to 65 years, from out-patient department and patients admitted in wards of the Department of TB and Chest Hospital were recruited. Follow up was done at 1st and 2nd month during which patients were actively enquired of any adverse drug reactions and the organ system affected were evaluated. RESULTS: In present study, 118 ADRs were experienced by 84 patients. Among the 84 ADRs victims, 60 patients showed different ADRs. Out of 84 patients, 75 patients developed ADRs within 30 days of the start of treatment of which most common ADR was gastrointestinal (46.6%) followed by liver problems (33.3%). CONCLUSION: Gastrointestinal tract is most commonly affected with ATT followed by hepatobiliary system. Utmost care has to be taken of these adverse effects so as to increase compliance to ATT and improve efficacy