Over a six-year period, 530 fire fatalities resulting from 398 fires were studied in the State of Maryland. The study had two major objectives: (1) to determine the specific cause of death by a detailed autopsy stud of fire victims, and (2) to determine the specific cause of fatality-producing fire by an on-the-scene fire investigation. The fire fatality study was limited to residential fires and to fatalities that occurred within 6 h of the fire. The results of the toxicological analysis show that (1) 60% of the victims had a carboxyhemoglobin value greater than or equal to 50% carbon monoxide saturation, (2) an additional 20% had elevated carboxyhemoglobin with preexisting cardiovascular disease, (3) 11% of the victims had severe burns, (4) 9% were unexplained and (5) 40% of the victims had positive blood alcohol levels with 30% of these meeting the legal definition of intoxication (blood alcohol ≥0.1%). The fire investigations confirmed that the predominant fatal scenario is the cigarette ignition of upholstered furniture or bedding. This scenario accounted for 47% of the fires and 44% of the victims. Alcohol also appears to be significant factor in this scenario.