The aim of this study was to examine the effect of different environmental, mechanical and individual factors associatedwith fatalities and serious injuries caused by work traffic accidents among cargo and passenger transport drivers (CPTD) inSpain. For this cross-sectional study, national data on work traffic accidents collected in Spain during the last 3 years wereanalyzed through a regression modeling approach, in order to predict the severity of traffic crashes involving CPTD. Usingbinary logistic regression analyses, it was found that the type of road and accident, the meteorological, light and vehicleconditions, individual characteristics and risky driving behaviors significantly predict the risk of fatal work traffic accidentsand serious injuries. These findings highlight the importance of combining organizational efforts with national road safetypolicies in order to generate a traffic safety culture among CPTD.