Abstract Battling serious injuries and long-term consequences in road traffic remains one important issue in the overall goal of resilient future road transport and its Vision Zero. Challenges of increasing personal transport in urban areas coupled with autonomous vehicles and shuttles, new mobility devices and the overall need to ensure the safety of vulnerable road users as well as all types of vehicle occupants’ require solid medical background knowledge paired with innovative engineering approaches. EU Horizon Europe is currently funding the ProtAct-Us consortium (2024-2027) that aims at protecting all Road User Groups from serious injury and long-term physical, cognitive and mental health consequences related to road crashes through innovatively interlinked research action between medical and engineering methods and approaches. ProtAct-Us works on the following goals and challenges: i) Medical data correlation, standardisation and classification of long-term consequences of road crashes; ii) Robust and reliable medical, epidemiological and engineering tools like agreed methods to collect information on long-term consequences, upgraded Human Body Models and virtual assessment methods for the extremities, head, neck and face allowing for effective countermeasure development for all road users; iii) Reduction of long-term consequences and related socio-economic cost of road crash related injuries for all road users. The ProtAct-Us solutions will influence new standards in respect of extending current injury codification system with relevant long-term aspects, allowing new physical as well as virtual safety assessment procedures and adaption of rules and regulations to be implemented. Finally, scientifically well-founded suggestion for future implementation into policy, regulatory, and standardization guidelines for an inclusive safety improvement approach for in- as well as post-crash will be provided.