Mortality rates are important outcome parameters after burn, and can serve as objective end points for quality control. Causes of death after severe burn have changed over time; in the international literature, multisystem organ failure is seen as the most important cause, but the exact distribution of causes of death remains unknown. Insight into underlying agents of mortality can be directive in research and prevention programmes. This comparison between results from the Rotterdam Burn Centre (RBC) and the American National Burn Repository (NBR) examines the most important predictive parameters for fatal outcome, i.e. age, total body surface area involved and presence of inhalation injury. Causes of death were attributed for all fatal outcomes treated in the RBC from 1996 to 2006. The mortality rate at the RBC was 6.9% and at the NBR was 5.6%, with almost no differences in age or total body surface area involved. The discrepancy in mortality rate might have been due to the high incidence of inhalation injury among the RBC population. However, the mortality rate at the RBC after admission with intention to treat decreased to 4.9%. The most frequent cause of death appeared to be multisystem organ failure, in 64.9% of cases; 93% of these had systemic inflammatory response syndrome at time of death and, in 45.9%, infection was deemed responsible for the fatal clinical deterioration (in 21.3% sepsis was proved and in 24.6% was highly suspected). To compare mortality rates between different burn centres and periods of time, uniform classifications are needed, particularly for presence of inhalation injury and for causes of death. Prevention of multisystem organ failure, by better management of infection and systemic inflammatory response syndrome, might do most to decrease mortality after burn.