ChAdOx1 nCoV-19 Vaccine (Covishield) has shown good efficacy data but the presence of non responders to the vaccine and the duration of protection conferred by the vaccine has not been clearly documented. To study the immunological response to ChAdOx1 nCoV-19 Vaccine among Health Care workers (HCWs) at a tertiary care hospital in Chennai. Materials and Methods: A Prospective study was conducted to analyze the duration of protection conferred by ChAdOx1 nCoV-19 Vaccine by testing the serum samples for Anti SARS IgG Antibody to spike protein by EUROIMMUNE ELISA Kit protocol by testing the pre vaccine sample, samples 2 weeks and 4 weeks following 1st dose,3 months and 6 months post 2 doses of vaccination and to study the association of waning immune response with comorbidities. A total of 265 Health Care Workers (HCWs) involving Nurses (35%), Doctors (32%), Technical staffs (17%) and House keeping staffs (16%) were included in the study. Majority were in age group of 41-50 Years (33%). Associated comorbidity was noticed in 19 % of HCWs. All 100% had sero conversion 4 weeks following Covishield but only 88 % had sero conversion 2 weeks following the 1st dose of Covishield. 100% of the HCWs had detectable levels of Anti SARS IgG antibody to spike protein 3 months following 2nd dose of Covishield but 6 months post 2nd dose only 90.5 % detectable levels of Anti SARS IgG antibody to spike protein. Among the 9.5% with waning immune response 68% had associated comorbidity like obesity (47%), Diabetes Mellitus (41%), Hyperlipidemia (6%) and Chronic lung disease (6%). It is important to maintain the protective antibody titers by vaccinating all the individuals with booster dose of the vaccine and considering population with comorbidities a high risk group for early priority.