Countries of South-East Europe show relatively low road safety performance among the EU Members. The objective of this paper is the exploration of a number of potential investments and interventions for the improvement of road safety in South-East European regions with regard to relative legislation, policy and institutional capacity. For the identification of the most appropriate road safety investments and interventions, a three step methodology was followed. Firstly, results of the, EU cofunded, ROSEE project concerning several aspects of road safety legislation, policy and institutional capacity in South-East European regions were exploited to identify the particular issues on which the proposed investments and interventions should focus. Then, relevant proposals and recommendations from the international bibliography were taken into account. Finally, original work was carried out by assessing and ranking selected road safety measures, programs, and policies. Specific road safety interventions were assessed and ranked based on three criteria, the estimated safety benefit related to the measure, the implementation cost and the implementation time needed for benefit. The overall results show that road safety legislation, policy and institutional capacity related investments and interventions are generally considered very effective for the improvement of road safety. On the other hand, it seems that most such investment proposals are considered relatively expensive to implement and effective on the long-term. These results were expected and are meaningful given that, based on international literature, the legislation, policy and institutional capacity are strategic aspects of road safety which, if taken into account at national level and in long-term, are considered highly effective. Specifically, the overall results show that investments and interventions considered to provide high safety benefit at low cost, in most partner countries, are the legislation for infrastructure safety management and the legislation for efficient enforcement. However, both types of investments need time to show their effect on the improvement of road safety. The analysis of the assessment results per country revealed important differences among South-East European regions that may be attributed to particular local characteristics and conditions.