Between 1990 and 2012, 2775 firefighters were killed in the line of duty. Myocardial infarction (MI) was responsible for approximately 40% of these mortalities, followed by mechanical trauma, asphyxiation, and burns. Protective gear, safety awareness, medical care, and the age of the workforce have evolved since 1990, possibly affecting the nature of mortality during this 22-year time period. The purpose of this study is to determine whether the causes of firefighter mortality have changed over time to allow a targeted focus in prevention efforts. The U.S. Fire Administration fatality database was queried for all-cause on-duty mortality between 1990 to 2000 and 2002 to 2012. The year 2001 was excluded due to inability to eliminate the 347 deaths that occurred on September 11. Data collected included age range at the time of fatality (exact age not included in report), type of duty (on-scene fire, responding, training, and returning), incident type (structure fire, motor vehicle crash, etc), and nature of fatality (MI, trauma, asphyxiation, cerebrovascular accident [CVA], and burns). Data were compared between the two time periods with a χ2 test. Between 1990 and 2000, 1140 firefighters sustained a fatal injury while on duty, and 1174 were killed during 2002 to 2012. MI has increased from 43% to 46.5% of deaths (P = .012) between the 2 decades. CVA has increased from 1.6% to 3.7% of deaths (P = .002). Asphyxiation has decreased from 12.1% to 7.9% (P = .003) and burns have decreased from 7.7% to 3.9% (P = .0004). Electrocution is down from 1.8% to 0.5% (P = .004). Death from trauma was unchanged (27.8 to 29.6%, P = .12). The percentage of fatalities of firefighters over age 40 years has increased from 52% to 65% (P = .0001). Fatality by sex was constant at 3% female. Fatalities during training have increased from 7.3% to 11.2% of deaths (P = .00001). The nature of firefighter mortality has evolved over time. In the current decade, line-of-duty mortality is more likely to occur during training. Mortality from burns, asphyxiation, and electrocution has decreased; but death from MI and CVA has increased, particularly in older firefighters. Outreach and education should be targeted toward vehicle safety, welfare during training, and cardiovascular disease prevention in the firefighter population.