Road safety is a major global health problem and no effort should be spared in trying to limit its impacts. Modeling road safety is a complex task, which needs to consider both the quantifiable impact of specific parameters, as well as the underlying trends that cannot always be measured or observed. Macroscopic data are often not available, or not in the form that they are desired. Therefore, it is often required to attempt to consider alternative sources of data, which may be correlated with the modeled phenomenon. The objective of this research is to investigate the suitability of alternative proxy variables for macroscopic road safety modeling, using three suitable exposure proxies: (i) number of vehicles in circulation, (ii) GDP and (iii) fuel consumption. Several structural time-series models have been developed for each proxy for two Mediterranean countries with many similar socio-economic characteristics: Greece and Cyprus. Based on the findings of this analysis, a number of observations can be drawn. Proxy variables can provide reasonable results, when exposure data are not available. Furthermore, even in two countries with many similarities the selected proxy measure differs. This suggests that the underlying conditions that make a variable a suitable proxy for exposure is complex and needs further investigation.