Background: Occupational heat-related mortality is not well studied and risk factors remain largely unknown. This paper describes the epidemiological characteristics of heat-related deaths among workers in the US 2000-2010. Methods: Fatality data were obtained at the Bureau of Labor Statistics from the confidential on-site Census of Fatal Occupational Injuries database. Fatality rates and risk ratios with 95% confidence intervals were calculated by year, sex, age group, ethnicity, race, state, and industry. Results: Between 2000 and 2010, 359 occupational heat-related deaths were identified in the U.S., for a yearly average fatality rate of 0.22 per 1 million workers. Highest rates were found among Hispanics, men, the agriculture and construction industries, the state of Mississippi, and very small establishments. Conclusions: This study provides the first comprehensive national profile of heat-related deaths in the U.S. workplace. Prevention efforts should be directed at small businesses and at industries and individuals with the highest risk.