Background & Objective: Active immunization (vaccination) is the main strategy adopted for the prevention of COVID-19 across the world. Vaccination is known to stimulate the human body to produce protective molecules and prepare for a possible encounter with the actual virus in the future. Antibody formation against the virus is one of the types of response to vaccination. The objective of the study was to analyze the antibody response of ChAdOx1- nCOV (CovishieldTM ) vaccine administration among health care workers (HCWs). Methods: The transfusion medicine department of SNMC, Agra enrolled health care workers who received ChAdOx1-nCOV (CovishieldTM) vaccine and obtained their informed consent. The enrollment for the study was done in January and February2021 (6 months follow-up was done till August 2021). The sampling was done on five points: day 0 (prior to the first dose), day 28 (prior to the second dose), day 56, day 120, and day 180 (from the first dose). Antibody against SARS-CoV-2 spike protein (mainly IgG) quantification was done by Roche (using Elecsys Anti-SARS-CoV-2 S kit) based on Electrochemiluminescence Immunoassay (ECLIA) at the department of microbiology, AMU, UP. Results: A total of 117 HCWs were enrolled in the study who received the vaccine between 16thJanuary to 18thFebruary 2021. 57 health care workers out of 117 (48.8%) had pre-existing antibodies on day 0 (group A) and 60 did not have any pre-existing antibodies (naïve participants, group B). The mean gap between the first and second dose of the vaccine was 29.8 days. The baseline (day 0) antibody levels in group A were 150.8332.2 U/mL compared to 0.47 0.14 U/mL in group B. The antibody response due to vaccination was significantly higher in group A than group B on the 28th day and 56thdays sampling. A total of 26 out of 117 enrolled HCWs (22.2%) reported a breakthrough infection of COVID-19 after 56thdays sampling. The breakthrough infection resulted in a significant rise in the antibody levels compared to participants who were never exposed toSARS-CoV-2 in group B (39 out of 60; naïve participants). Interpretation and Conclusion: We concluded that the antibody production in response to vaccination, was significantly higher in a group of participants who had previous exposure to the virus before vaccination. Exposure to the virus after a complete schedule of vaccination also induced a significant rise in antibody levels. The antibody response in naïve participants who hadboth doses of the vaccines (never exposed to the virus) had significantly lower levels at 180 days compared to their antibody peak at 56 days.