AbstractBackground Information about the burden of (non-fatal) road traffic injury is very useful to further improve road safety policy. Previous studies calculated the burden of injury in individual countries. This paper estimates and compares the burden of non-fatal serious road traffic injuries in six EU countries/regions: Austria, Belgium, England, The Netherlands, the Rhône region in France and Spain. Methods It is a cross-sectional study based on hospital discharge databases. Population of study are patients hospitalized with MAIS3+ due to road traffic injuries. The burden of injury (expressed in years lived with disability (YLD)) is calculated applying a method that is developed within the INTEGRIS study. The method assigns estimated disability information to the casualties using the EUROCOST injury classification. Results The average burden per MAIS3+ casualty varies between 2.4 YLD and 3.2 YLD per casualty. About 90% of the total burden of injury of MAIS3+ casualties is due to lifelong consequences that are experienced by 19% to 33% of the MAIS3+ casualties. Head injuries, spinal cord injuries and injuries to the lower extremities are responsible for more than 90% of the total burden of MAIS3+ road traffic injuries. Results per transport mode differ between the countries. Differences between countries are mainly due to differences in age distribution and in the distribution over EUROCOST injury groups of the casualties. Conclusion The analyses presented in this paper can support further improvement of road safety policy. Countermeasures could for example be focused at reducing skull and brain injuries, spinal cord injuries and injuries to the lower extremities, as these injuries are responsible for more than 90% of the total burden of injury of MAIS3+ casualties.