The economic assessment of intervention projects at hazardous locations aims to maximize road safety benefits by exploiting the full potential of limited available funds for road safety. The study presents a case study for the economic assessment of road safety schemes in crash prone locations in rural highways in Viotia and Imathia sub-regions in Greece, using crash prediction models from the AASHTO Highway Safety Manual. The models were suitably adjusted, calibrated and adapted according to data availability, and were used, along with findings from road safety inspections of the locations under consideration, to estimate expected reductions in fatalities and casualties due to the implementation of specific road safety schemes. Road safety benefits were then translated into monetary terms, and, taking also into account construction and maintenance costs for each scheme, the economic rate of return (ERR) of the project was estimated. The economic rates of return were estimated at 27.1% for Viotia sub-region and 18.2% for Imathia sub-region, thus demonstrating the very high cost effectiveness of road safety intervention schemes in hazardous locations.