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Introduction: Firefighters are exposed to toxic agents in combustion products at fire scenes increasing their risk for cancer and cardiovascular disease. Inconsistent findings in previous research examining excess heart disease and cancer mortality have led to the need for further investigation of cause-specific death among firefighters.Objective: Using death certificate data, we tested the hypotheses that there is no difference in the likelihood of cancer and cardiovascular mortality between firefighters and a matched population of non-firefighters from the general population.Methods: Firefighter death records (n=2,818) were exactly matched to four non-firefighter (n=11,272) death records on age at time of death, sex, race, ethnicity and year of death between 1985-2013.Underlying cause of death was coded using the 9th and 10th revision of the International Classification of Diseases (ICD). Mortality odds ratios and 95% confidence intervals comparing firefighters to non-firefighters were calculated using conditional logistic regression to account for matching.Results: The risk of death due to all malignant cancers was significantly higher for firefighters than non-firefighters (OR: 1.19; 95% CI 1.08, 1.30). Firefighters had high risks of mortality due to malignancies of the buccal cavity and pharynx (OR 2.15, 95% CI 1.19, 3.79), other parts of the buccal cavity (OR 4.00, 95% CI 1.07, 14.96), pharynx (OR 2.26, 95% CI 1.05, 4.65), pancreas (OR 1.45, 95% CI 1.01, 2.06), and kidney (OR 1.84, 95% CI 1.17, 2.83). Deaths due to malignancies of other and unspecified sites (OR 1.27, 95% CI 1.02, 1.56) were also elevated among firefighters, due specifically to connective tissues (OR 2.5, 95% CI 1.01, 5.86) and brain and other parts of the nervous system (OR 1.98, 95% CI 1.23, 3.12). There was no difference in risk for heart disease deaths, including ischemic heart disease, between the two groups. However, the risks for undefined types of circulatory system deaths (OR 0.80, 95% CI 0.68, 0.94), specifically cerebrovascular disease (OR 0.82, 95% CI 0.67, 0.99) were significantly lower among firefighters than non-firefighters. Accidental poisoning deaths were also significantly lower (OR 0.43, 95% CI 0.43, 0.96) among firefighters.Conclusions: Deaths due to specific malignant cancers were found to be statistically higher in Indiana firefighters than non-firefighters. The study suggest the importance of early and effective health-promoting prevention strategies among firefighters.Clinical Significance: Firefighters need access to clinical evaluations focused on modifiable occupational and lifestyle risk factors. Biometric, fitness, psychological and self-reported data gathered during these examinations should be utilized for the development and assessment of specific occupational risk intervention programs.