To investigate the association between sleep apnea syndrome (SAS) and automobile accidents, and to evaluate potential underlying mechanisms, we prospectively recruited 60 consecutive patients with SAS (apnea-hypopnea index, 58 +/- 3 h-1) and 60 healthy control subjects, matched for sex and age. The number of automobile accidents during the past 3 yr was obtained from participants and insurance companies. We quantified the degree of daytime sleepiness (Epworth scale), anxiety and depression (Beck tests), and we assessed the level of vigilance (PVT 192) and driving performance (Steer-Clear). Patients had more accidents than control subjects (OR: 2.3; 95% CI: 0.97 to 5.33) and were more likely to have had more than one accident (OR: 5.2; 95% CI: 1.07 to 25.29, p < 0.05). These differences persisted after stratification for km/yr, age, and alcohol consumption. Patients were more somnolent, anxious, and depressed than control subjects (p < 0.01), and they had a lower level of vigilance and poorer driving performance (p < 0.01). Yet, we did not find any correlation between the degree of daytime sleepiness, anxiety, depression, the number of respiratory events, nocturnal hypoxemia, level of vigilance, or driving simulator performance and the risk of automobile accidents among SAS patients. In conclusion, patients with SAS have an increased risk of automobile accidents. None of the clinical or physiological markers commonly used to define disease severity appear able to discriminate those patients at higher risk of having an automobile accident.