Yellow fever (YF), an acute infectious disease, is endemic in the north and central-west of Brazil. This disease can be prevented by the use of a vaccine. In Brazil, four fatal adverse events have been associated with the YF vaccine used in the country (17DD vaccine). We briefly describe the last two fatalities, and estimate the risk of 17DD-associated fatal adverse events under different epidemiological scenarios. Controversies regarding the appropriate denominator that enters the estimation of risk serve as a motivation for each proposed scenario. The statistical procedures used show optimum behaviour when assessing the risk of rare events. Risk estimates vary from 0·043 (95% CI 0·017–0·110) to 2·131 (95% CI 0·109–12·071) fatalities per million doses administered. The robust estimates of the risk of fatal adverse events we present constitute an important element in future risk–benefit analysis and point to the need for good quality vaccine coverage and adverse-events surveillance data to assess the risk of vaccination. Although vaccination of YF endemic regions is necessary to maintain low disease prevalence, preventive administration of YF vaccine to the entire population should be cautiously analysed.