The role of medical conditions in crashes is a topic of public debate. Some studies suggest that there has been a reduction in road traffic crashes subsequent to the medical restrictions introduced on drivers with medical deficiencies. As in today's society the car is an important factor for independence and socialization, it seems important to consider whether diseases or consumption of drugs increase the risk of causing a road crash in comparison to well-known major crash risk factors. A case–control study was conducted (733 injured drivers). The cases were subjects who were partly or totally responsible for their crash. The 304 controls were the non-responsible drivers. Diseases and medicine consumption were analyzed using logistic regression models. Cases were characterized by a higher percentage of young men. They were more frequently affected by fatigue, as were subjects who had consumed alcohol. A higher risk in subjects suffering from hypertension is observed (adjusted odds ratio [adjOR] = 3.82; 95%CI = [1.42–10.24]). An association between antidepressant consumption and responsibility appeared (adjOR = 3.61; 95%CI = [1.30–10.03]). Conclusion Medical factors associated with responsibility were arterial hypertension and antidepressant consumption. Other medical conditions do not seem to play a preponderant role comparing to individual behaviours.