Objective: To describe the magnitude and characteristics of crashes and drivers involved in head-on crashes on two-way interurban roads in Spain between 2007 and 2012, and to identify the factors associated with the likelihood of head-on crashes on these roads compared with other types of crash. Methods: A cross-sectional study was conducted using the National Crash Register. The dependent variables were head-on crashes with injury (yes/no) and drivers involved in head-on crashes (yes/no). Factors associated with head-on crashes and with being a driver involved in a head-on crash versus other types of crash were studied using a multivariate robust Poisson regression model to estimate proportion ratios (PR) and confidence intervals (95% CI). Results: There were 9,192 head-on crashes on two-way Spanish interurban roads. A total of 15,412 men and 3,862 women drivers were involved. Compared with other types of crash, head-on collisions were more likely on roads 7 m or more wide, on road sections with curves, narrowings or drop changes, on wet or snowy surfaces, and in twilight conditions. Transgressions committed by drivers involved in head-on crashes were driving in the opposite direction and incorrectly overtaking another vehicle. Factors associated with a lower probability of head-on crashes were the existence of medians (PR = 0.57; 95%CI: 0.48-0.68) and a paved shoulder of less than 1.5 meters (PR = 0.81; 95%CI: 0.77-0.86) or from 1.5 to 2.45 meters (PR = 0.90; 95%CI: 0.84-0.96). Conclusions: This study allowed the characterization of crashes and drivers involved in head-on crashes on two-way interurban roads. The lower probability observed on roads with median strips point to these measures as an effective way to reduce these collisions