Introduction: Tuberculosis (TB) continues to remain one of the most pressing health problems, with India being the highest TB burden country. India has adopted and enforced Directly Observed Treatment Short course (DOTS) strategy to combat TB. The first line medicines in DOTS are known to cause adverse effects like gastritis, hepatotoxicity and skin allergies. This study was done to determine the occurrence of such adverse effects in patients under DOTS therapy and to assess their impact if any on patient compliance. Methods: A hospital based cross-sectional observational study was carried out on all newly diagnosed cases of TB as well as those registered in DOTS centre in Chest and TB department of a tertiary care hospital. A structured proforma was used to collect information regarding adverse effects of medicines under DOTS. Biochemical tests were done after voluntary consent. Results: A total of 168 patients (132 male, 36 female) were interviewed for the study. Patients reported adverse drug effects which mainly involved Gastro-intestinal system (39%), Genito-urinary system (32%), Musculo-skeletal system (13%), Central Nervous System (7%), Dermatological (6%), Vestibulo-ocular system (3%). 68.5% of the patients gave consent for biochemical investigations out of which Serum bilirubin (direct) was raised in 52%, Serum albumin was below normal limit in 59% and ESR was raised in 59%. Conclusion: Majority of adverse effects were mild. Most commonly encountered symptoms were abdominal. Most patients reported adverse drug effects to be the most likely cause to stop the treatment. Special interventions to cure these mild adverse effects can lead to increased patient compliance and hence a better cure rate. Results also showed that family plays the most important role as a support to combat the illness.