The purpose of this study was to investigate the frequency, circumstances, demographics, and causes of death of infants dying while seated in car safety seats. A retrospective review of a pediatric autopsy database at a specialist center over a 16-year period was undertaken to identify any infant deaths (aged <1 year), in whom death occurred while seated in a car safety seat. Fourteen car seat-associated deaths were identified from a total of 1,465 coronial infant autopsies (0.96 %). Four involved infants were being appropriately transported in the car seat, all of whom had a medical underlying cause of death (one infection and three congenital heart disease). The majority (10 cases; 70 %) occurred while car seats were being inappropriately used, outside of the car, including as an alternative to a cot or high-chair. Five of these infants died of explained causes, but four deaths remained unexplained after autopsy, and in one no cause of death was available. There were no cases of previously healthy infants dying unexpectedly in a car seat when it was being used appropriately, and in this series there were no cases of traumatic death associated with car seats, either during road traffic accidents, or from falling or being suspended from a car seat. Infant deaths in car seats are rare. These data support the recommendation that car seats be used only for transport and not as alternatives for cots or high-chairs. More research is required to investigate the effect of travel in car seats on infants with underlying conditions. There appears to be no increased risk of unexpected deaths of healthy infants transported appropriately in car seats.