Aim:  To determine the Health-related Quality of life and Self-Esteem of patients who have undergone Dots regimen for pulmonary tuberculosis in Rntcp centre Villupuram district. Objectives: (i) To determine the Health-related Quality of Life and Self-Esteem of patients who have undergone DOTS regimen for pulmonary tuberculosis. (ii) To compare the scores of Health-related Quality of Life and Self-Esteem of patients who have undergone DOTS regimen for pulmonary tuberculosis at different intervals. (iii) To correlate the mean differed scores of Health-related quality of life and Self-Esteem of   patients who have undergone DOTS regimen for pulmonary tuberculosis. (iv) To associate the selected background variables with the mean differed scores of Health-related Quality of Life and Self-Esteem of patients who have undergone DOTS regimen for pulmonary tuberculosis. Methodology:  Non experimental Descriptive Survey method was adopted.100 samples selected by using non-probability purposive sampling technique. Formal administrative permission obtained from concerned authorities and informed written consent obtained from the sample. Background variables data was collected and Health-related quality of life and Self-Esteem was assessed by FACIT-TB Health-Related Quality of Life Scale and SERTHUAL Self-Esteem Scale respectively by using structured interview schedule from selected samples at 0, 3rd  and 6th  month. Results: In level of Health-related quality of life there is highest level of frequency is moderate QOL 79 (79%), in 0 month and Good QOL 59 (59 %) and 74 (74%) in 3rd and 6th month respectively. In level of Self-Esteem the highest level  frequency at positive general Self-Esteem is 57 (57%), 74 (74%) and 81 (81%) at 0, 3rd and 6th month respectively. The overall Health-related quality of life score and Self-Esteem score, there is a significant, positive, moderate correlation. It indicates quality of life score increases and the Self-Esteem score also increases moderately. Conclusion: The result of the study revealed that Health-Related Quality of Life and Self-Esteem was improved after the completion of the treatment. There was a moderate positive correlation between the Health-Related Quality of Life and Self-Esteem among patients who have undergone DOTS regimen.