The present Special Issue of ATS is dedicated to the 8th Road Safety and Simulation International Conference 2022 (RSS2022) that took place on 08-10 June 2022 at Zappeion Megaron in Athens organized by the National Technical University of Athens (NTUA) and the Hellenic Institute of Transportation Engineers (HITE). The main aim of the Conference was to improve upon the existing scientific knowledge in the area of road safety and contribute to reduce the number of accident fatalities and injuries occurring worldwide, through the promotion of state-of-the-art innovative road safety research and applications in the digital era. This Special Issue on RSS2022 provides a synthesis of thirteen (13) high-quality scientific papers, focusing on innovative road safety measures addressing key research fields, namely roadway infrastructure, safety modelling, human factors, vulnerable road users and automated driving.