Background: Tuberculosis is one of the leading causes of mortality and morbidity around the world, infecting approximately 8 billion people, with an annual death rate of close to 1 million. The present study was conducted to evaluate the impact of tuberculosis treatment on health related quality of life (HRQoL) of patients with active and inactive tuberculosis by evolving HRQoL questionnaire (SF-36v2). Methodology: A prospective follow-up study was conducted for total 70 patients (56 men and 14 women) diagnosed with tuberculosis (TB) in Navodaya Medical College Hospital & Research Centre, Raichur for a period of 6 months. The HRQoL of TB patients was assessed in three phases: at the onset of treatment, at one month (middle of intensive phase) and two months (end of intensive phase), after the initiation of anti-tuberculosis therapy. Results: A total of 70 patients completed the SF-36v2 questionnaire at the start of their treatment. Out of these, 53 and 41 completed the questionnaire at the second and third follow-ups, respectively. The mean physical component summary (PCS) scores at the start of the treatment, after one month and at the intensive phase were 42.09 ± 16.77, 53.89 ± 13.64 and 65.24 ± 12.86, respectively. Similarly, the mean mental component summary (MCS) scores at the start of the treatment, after one month and at the intensive phase were 43 ± 17.07, 52.19 ± 14.12 and 62.17 ± 15.12, respectively. Conclusion: The HRQoL improved with the treatment, the scores on component summary measures revealed the improvement of both physical and mental health among study patients at the end of intensive phase.