BackgroundCOVID-19 vaccines have been used across Japan since 17 February 2021, and as of 17 April 2022, 1690 deaths potentially caused by vaccine-related adverse effects have been reported to the Ministry of Health, Labour and Welfare. However, the causal relationship between vaccination and death could not be fully evaluated because of a lack of sufficient information. MethodsAutopsy cases in which deaths occurred within seven days after COVID-19 vaccination in Tokyo Metropolis and were handled by medical examiners were selected (n = 54). Age, sex, vaccine-related information, cause of death, and possible causal relationship between vaccination and death were examined. ResultsThe mean age of the deceased individuals was 68.1 years, and the study sample consisted of 34 males (63.9%) and 20 females (37.0%). Thirty-seven and six individuals received Comirnaty and Spikevax, respectively (68.5% and 11.1% respectively). The manner of death included natural (n = 43), non-natural (n = 8), and undetermined (n = 3). The most frequent cause of death was ischemic heart disease (n = 16). Regarding causal relationships, 46 cases (85.2%) did not show a causal relationship to vaccination, except for myocarditis (n = 3), thrombosis-related death (n = 4), and others (n = 1). ConclusionAlthough many cases of deaths after COVID-19 vaccination in this study showed no definite causal relationship between the vaccination and deaths, some cases showed possible adverse events such as myocarditis. Autopsies are essential for detecting vaccine-related deaths, and the Japanese death investigation system needs to be reinforced from this viewpoint.