In the contest of the EU program “ Road Safety in EU: the 1997-2001 program”, the “IASP” project, proposed by the Province of Catania with the scientific support of the Department of Civil and Environmental Engineering of University of Catania, was approved and co-funded by European Commission (DG TREN). A methodological approach for the safety evaluation of two-lane rural highway segments that uses both analytical procedures referring to road safety inspection processes and alignment design consistency models is presented. Road safety inspections (RSI) are recognized as an effective tool for identifying safety issues. However, due to the subjective nature of the process, they may give rise to disagreements which limit their effectiveness. A RSI procedure aimed at improving the effectiveness and the reliability of the methodology was defined. Many studies show that safety evaluations based on the analysis of alignment design consistency can be effective in identifying hazardous road locations. The proposed approach makes use of theoretical-experimental models for the evaluation of alignment design consistency. A safety index (SI) that quantitatively measures the relative safety performance of a road segment is calculated from the procedure. The SI is formulated by combining three components of risk: the exposure of road users to road hazards, the probability of a vehicle being involved in an accident and the resulting consequences should an accident occur. Validation of the procedure was carried out on a sample of roads by a comparison of the risk rank obtained using the SI and accident history. The SI was assessed in 30 segments chosen from a sample of two-lane rural highways in Italy and the actual accident situation was obtained with the EB procedure. Spearman’s rank-correlation was used to determine the level of agreement between the rankings obtained using the two techniques. The results from the Spearman’s rank-correlation analysis validate the SI, indicating that the ranking from the SI scores and the EB estimates agree at the 99.9% level of significance with a correlation coefficient equal to 0.8.