Global vaccine development efforts have been accelerated in response to the devastating COVID-19 pandemic. The study aims to determine the seroprevalence of SARS-CoV-2 IgG antibodies among vaccine-naïve healthcare workers and to describe the impact of vaccination roll-out on COVID-19 antibody prevalence among the health care centers in tertiary care centers in South India. Serum samples collected from vaccinated and unvaccinated health care workers between January 2021 and April 2021were subjected to COVID-19 IgG ELISA, and adverse effects after the first and second dose of receiving the Covishield vaccine were recorded. The vaccinated group was followed for a COVID-19 breakthrough infection for a period of 6 months. Among the recruited HCW, 156 and 157 participants were from the vaccinated and unvaccinated group, respectively. The seroprevalence (COVID-19 IgG ELISA) among the vaccinated and unvaccinated Health Care Workers (HCW) was 91.7% and 38.2%, respectively, which is statistically significant. Systemic and local side-effects after Covishield vaccination occur at lower frequencies than reported in phase 3 trials. Since the COVID-19 vaccine rollout has commenced in our tertiary care hospital, seropositivity for COVID-19 IgG has risen dramatically and clearly shows trends in vaccine-induced antibodies among the health care workers.