OBJECTIVES The aim of the study was to determine if differences in clinical diagnosis versus autopsy findings concerning the cause of death in polytrauma fatalities would be detected in 19 cases of fatal polytrauma from a Level 1 trauma centre. METHODS Clinical diagnoses determining the cause of death in 19 cases of fatal polytrauma (2007 - 2008) from a Level 1 trauma centre were correlated with autopsy findings. RESULTS In 13 cases (68%), the clinical cause of death and the cause of death as determined by autopsy were congruent. Marginal differences occurred in three (16%) patients while obvious differences in interpreting the cause of death were found in another three (16%) cases. Five fatalities (three with obvious differences and two with marginal differences) were remarked as early death (1-4 h after trauma) and one fatality with marginal differences as late death (>1 week after trauma). Obvious and marginal discrepancies mostly occurred in the early phase of treatment, especially when severely injured patients were admitted to the emergency room undergoing continued cardiopulmonary resuscitation, i. e. limiting diagnostic procedures, and thus the clinical cause of death was essentially determined by basic emergency diagnostics. CONCLUSIONS Autopsy as golden standard to define the cause of death in fatal polytrauma varies from the clinical point of view, depending on the patient's pre-existing condition, mechanism of polytrauma, necessity of traumatic cardiopulmonary resuscitation, survival time, and thus the possibility to perform emergency diagnostics. An autopsy should be performed at least in cases of early fatal polytrauma to help establishing the definite cause of death. Moreover, autopsy data should be included in trauma registries as a quality assessment tool.