Objective The objective of this study was to assess the ongoing pharmacovigilance of coronavirus disease-19 (COVID-19) vaccines in the Nepalese context based on the available preliminary adverse drug reaction (ADR) reports and suggest approaches for strengthening pharmacovigilance mechanisms. Methods Currently, many COVID-19 vaccines are under advanced development and some have begun to be administered. In Nepal, the vaccination programme was initiated with Oxford/ AstraZeneca COVID-19 AZD1222 (Covishield) vaccine on January 27th targeting frontline health-care professionals, sanitary staff and security workers. Newspaper reports and ADR reports received at a regional pharmacovigilance centre in Nepal were analysed. Nepal initiated a national pharmacovigilance programme 15 years back and has 14 functioning regional pharmacovigilance centres. The authors examine the strengths and challenges facing the current pharmacovigilance system in ensuring the safety of COVID-19 vaccines. Key findings The news coverage has not mentioned any deaths till date with COVID-19 vaccination. Some patients reported vomiting, urticaria and sudden increase in blood pressure. Few people suffered from headache, fever and myalgia after being vaccinated. A vaccine, approved in an accelerated manner may have safety concerns. The vaccine may cause several types of reactions, but serious reactions have not been reported. Occurrence of adverse effects due to the vaccine is being studied. Conclusions Involving key stake holders, training health professionals and strengthening existing reporting procedures are important. Developing a system of reporting and analysing ADRs daily can help generate actionable intelligence to improve the safety of the vaccination programme. Establishing functioning communication channels between regulatory authorities and other stakeholders is crucial.