Objective: The objective of this report is to provide a comprehensive description of fatigue in US railroad workers employed in safety-sensitive positions. Methods: Five survey studies were conducted between 2006 and 2011 on maintenance of way employees, signalmen, dispatchers, train & engine (T&E) employees, and T&E employees engaged in passenger service. These studies were reanalyzed and compared with regard to work schedules and sleep patterns. Fatigue exposure was determined by analysis of work schedules and sleep patterns with a fatigue model, the Fatigue Avoidance Scheduling Tool (FAST). Results: Twelve different schedules of work exist in the five groups of railroad employees. Work schedules largely determine sleep patterns, which, in turn, determine fatigue exposure. T&E crews and dispatchers have the highest fatigue exposure, but these two groups have considerably less fatigue exposure than T&E crews who were involved in accidents. Passenger service T&E employees have the least fatigue exposure, even though the distribution of work time is highly similar to that of T&E employees. This difference in fatigue exposure may be due to the greater predictability of work for the passenger service T&E. Human factor accident probability and the cost of human factor accidents increase with fatigue exposure. The risk (probability × cost) of a human factor accident increases exponentially with fatigue exposure. Conclusions: A methodology has been developed for studying the work schedules and sleep patterns of railroad workers. This methodology allows for the collection of data which makes it possible to identify differences in sleep patterns as a function of both work group and work schedule. Future work on fatigue in occupational groups should focus on similar methods to expand our knowledge of the role of work schedules on sleep, fatigue, and accident risk.