Previous studies have suggested that patients with obstructive sleep apnea syndrome (OSAS) are at an increased risk of motor vehicle accidents (MVAs). This study is the first systematic investigation of MVA risk among Japanese drivers with obstructive sleep apnea syndrome (OSAS). We investigated the rate of MVAs in the preceding 5 years and dozing off at the wheel in Japanese male OSAS drivers (n = 616, mean [S.D.] age: 46.3 [10.1] years old) and age-matched male controls (n = 600), and the characteristics of OSAS patients who experienced multiple MVAs as well as the effectiveness of continuous positive airway pressure (CPAP) treatment in reducing MVA risk. The odds ratio of MVA in the OSAS group compared to a general population was 2.36. Multivariate logistic regression analysis revealed that MVA was significantly associated with either subjective sleepiness beyond normal limits (Epworth sleepiness scale: ESS > or = 11) or serious respiratory disorders (apnea hypopnea index: AHI > or = 40). AHI scores were significantly higher in the group with multiple MVAs than in those with a single MVA, despite the ESS score in the former group being significantly lower. CPAP treatment was effective for reduction of MVA. The MVA rate among OSAS patients in the research area was significantly higher than that among the controls. Subjective excessive daytime sleepiness and severity of OSAS are independently associated with the occurrence of MVA. In conclusion, early diagnosis and treatment of OSAS drivers especially with serious respiratory disorder should be made to prevent multiple MVAs.