Despite its severity, anaphylaxis carries a low mortality rate of less than 1%, making the cohort seen in the forensic pathology setting a small and unique subset of the majority of cases of anaphylaxis in the community. Clinically, cardiovascular disease has been recognized as a risk factor for fatal anaphylaxis; however, there is scant forensic pathology research investigating this risk factor, whereas autopsy textbooks emphasize physical respiratory changes seen in the broader clinical cohort. This 20-year retrospective study examined all fatal anaphylactic deaths in the state of Queensland, Australia, to document the underlying disease of the cases, tryptase levels, triggers, and postmortem findings. Our study found that cardiovascular disease was prevalent in 83.3% of cases of fatal anaphylaxis. Although asthma was prevalent in food-related fatal anaphylaxis (60%) in our cohort, it was poorly represented overall (28%), in contrast to clinical research. Additionally, only 43% of cases showed respiratory changes that were greater than mild. Our findings emphasize the difference between the clinical and postmortem anaphylaxis cohorts, and provide autopsy evidence of a potential role of cardiovascular disease in fatal anaphylaxis.