The present study aims serial four year assessment of CD4 cell response after initiation of anti-retroviral therapy (ART) in patients with HIV/AIDS attending Osmania General Hospital, Hyderabad. It was a retrospective hospital based observational study. We included 110 HIV/AIDS who were on ART. Data was collected over a period of 04 years from 2005 to 2008 in the ART Centre, Upgraded Department of General Medicine, Osmania General Hospital. Data regarding CD4 cell count over 4 years was assessed for mean CD4 cell count, trends, age and sex wise distribution. All patients were on ART as per National Aids Control Organisation (NACO) guidelines. Complete blood picture, serum creatinine, blood urea, serum electrolytes, liver function tests, sputum for acid fast bacilli, chest radiography, CD4 cell count in all patients, fine needle aspiration and biopsy (if necessary), magnetic resonance imaging (if necessary), computerized tomography (if necessary), colonoscopy (if necessary). The present study showed mean CD4 count improvement of 128.78 cells/mm3 after 6 months of initiation of ART, 24.77cells /mm3 after 1 year, additional 67.53 cells/mm3 after 2nd year and after 3rd year 5.59cells/mm3 from base line CD4 cell count. Improvement in CD4 count was almost equal in both male and female and in age group <25 years and above 40 years age group also. Mean CD4 cell count improvement of 240.31 cells/mm3 in females and 220.54 cells/mm3 in males to the baseline after 3 years of treatment with ART. Present study clearly shows definite improvement in CD4 cell count after ART was more than 100% irrespective of age and sex. Regular intake of drugs will improve immunologic response. Therefore strict adherence to ART /regular counseling sessions at ART centres should be stressed upon. [J Med Allied Sci 2016; 6(2.000): 68-71]