The objective of this research is to investigate cost-benefit assessment techniques for road safety measures, including methodological issues, data availability and data quality, through three case-studies in Greece. The first part of the paper concerns a review of the available methods for calculating the efficiency of road safety measures, in terms of safety effect (accidents and casualties reduction) as well as other related effects (traffic, environmental etc.). Additionally, a detailed description of the calculation process of the various components of generalized and human accidents costs in Greece is presented. The second part of the paper reports the results of cost-benefit analysis application in three case studies in Greece; one on the implementation of traffic calming measures at municipal level, one on the upgrading of selected sections of the National Road network into motorways, and one on the nationwide intensification of speed and alcohol enforcement. Conclusions concern both the efficiency of the measures and the assessment process. Furthermore, the main difficulties encountered in the above case studies and the alternatives for dealing with them are discussed.