Aims and objectives: In coronavirus disease-2019 (COVID-19) disease, there is no antiviral drugs, hence, Covishield vaccination is the best way of prevention. In India, after two doses of vaccination drive, there has been reports of adverse drug events (ADEs) but there has been creation of misinformation about the safety of the vaccine in some reports. Only few studies are available to monitor the ADEs after the third dose of COVID-19 vaccine. Therefore, this study was planned to establish the safety of Covishield vaccine after three doses. Materials and methods: An observational, non-interventional, retrospective study based on surveillance was conducted to assess the safety of Covishield vaccine after three doses. The vaccine was given by Department of Immunization, Preventive and Social Medicine Department, Sri Guru Ram Das Hospital, Amritsar. Subjects were instructed to record solicited/unsolicited adverse reactions in the proforma provided to them in English/Hindi/Punjabi language and were instructed to record ADEs up to 42 days post-vaccination period. Results: A total of 1,364, 1,340, and 1,296 subjects were given the first, second, and third doses of vaccine. The most common solicited ADEs after the third dose with duration was pain at injection site in 48.1% of subjects for 1 day, mild fever temperature ≤100.5°F for 2 days, malaise in 13.1%, injection site swelling in 7%, headache in 5%, myalgia in 4%, chills in 2.5%, rigors in 1.4% of the subjects for 1 day. Adverse drug events seen in subjects with comorbidities were 62.2% after the first dose, 26.2% after the second dose, and 11.4% after the third dose showing a significant reduction in ADEs after each dose. Conclusion: Covishield vaccine is safe and effective after the third dose as compared with the second and first dose.