A population-based case-control study was carried out to examine driver risk factors for sleep-related motor vehicle crashes. Cases included 312 drivers involved in recent North Carolina crashes and identified on police reports as asleep at the time of the crash and 155 drivers identified as fatigued. Controls were 529 drivers also involved in recent crashes but not identified as asleep or fatigued, and 407 drivers not involved in recent crashes. All drivers were contacted for brief telephone interviews. Results showed that drivers in sleep-related crashes were more likely to work multiple jobs, night shifts, or other unusual work schedules. They averaged fewer hours sleep per night, reported poorer quality sleep, were less likely to feel they got enough sleep, were sleepier during the day, drove more often late at night, and had more prior instances of drowsy driving. Compared to drivers in non-sleep-related crashes, they had been driving for longer times, been awake more hours, slept fewer hours the night before, and were more likely to have used soporific medications. Knowledge of specific risk factors for sleep-related crashes is an important first step in reducing the thousands of deaths and injuries each year in the US attributed to drowsy driving.