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To analyze characteristics of, and trends in, work-related carbon monoxide (CO) fatalities in the US.Records of unintentional, non-fire related fatalities from CO exposure were extracted from the Bureau of Labor Statistics' Census of Fatal Occupational Injuries and the Occupational Safety and Health Administration's Integrated Management Information System for years 1992–2008 and analyzed separately.The average number of annual CO fatalities was 22 (standard deviation = 8). Fatality rates were highest among workers aged ≥65, males, Hispanics, winter months, the Midwest, and the Fishing, Hunting, and Trapping industry subsector. Self-employed workers accounted for 28% of all fatalities. Motor vehicles were the most frequent source of fatal CO exposure, followed by heating systems and generators.CO has been the most frequent cause of occupational fatality due to acute inhalation, and has shown no significant decreasing trend since 1992. The high number of fatalities from motor vehicles warrants further investigation. Am. J. Ind. Med. 56:1280–1289, 2013. © 2013 Wiley Periodicals, Inc.