Background: Adverse events following immunization (AEFI) is defined as any untoward medical occurrence which follows immunization and which does not necessarily have a causal relationship with the usage of the vaccine. Break-through infections are referred to as antigen or SARS-CoV-2 RNA positivity of respiratory specimens more than 14 days after receiving all recommended doses. Aim: The study was conducted to identify adverse events and break-through infections following the precautionary dose of the COVID-19 vaccine among healthcare workers. Methodology: The study was designed as a cohort event monitoring; all healthcare professionals who received COVID-19 precautionary dose from the study site were included in the study. The study population was actively followed for any adverse event following immunization (AEFI) through telephonic contact (within 30 days of post-vaccination). Reported adverse events were carefully scrutinized and evaluated by the AEFI investigation team of the study site. Results: Out of 1232 vaccine beneficiaries, a total of 359 (29.14%) individuals were reported with 385 AEFIs. Of which 138 (38.44%) individuals were laboratory-confirmed (RTPCR positive) breakthrough cases. Less severity and low morbidity were observed among all the breakthrough cases. According to the WHO’s new causality assessment algorithm, 183 (47.53%) events were vaccine product-related and 202 (52.46%) were co-incidental events. Conclusion: There was a prevailing outbreak of COVID-19 infection in the study site, which resulted in many breakthrough infections soon after immunization. Initially, all breakthrough infections were misleading as vaccine-related events, where this study helped to break the concerns among the study population.