The objective of this research is to develop and test a framework for efficiency assessment of road safety measures and evaluate its use in decision-making. An exhaustive review of standard methodologies and practices related to cost-effectiveness and cost-benefit analyses is carried out for that purpose. Moreover, a number of case-studies are performed, concerning the efficiency assessment of various road safety measures in different countries, covering different types of road safety measures (user-, vehicle- or infrastructure-oriented, policy or enforcement and so on), ranging from national to local levels of implementation and including both ex ante and ex post evaluations. From the results conclusions are drawn on the efficiency of different road safety measures and the related determinants. Furthermore, the case-studies reveal a number of methodology and data issues, for which further research is required. The procedures and barriers involved in the use of efficiency assessment techniques at different levels of decision-making are also highlighted, by means of feedback received during and after the various case-studies. On the basis of these results, a framework for the promotion, implementation and evaluation of efficiency assessment in road safety decision-making is proposed. A particular set of recommendations is also presented regarding the treatment of barriers (fundamental, institutional or technical) within the efficiency assessment itself and the related decision-making process.