ABSTRACT: Importance:Ambient fine particulate matter (PM2.5) air pollution is associated with increased risk of several causes of death. However, epidemiologic evidence suggests that current knowledge does not comprehensively capture all causes of death associated with PM2.5 exposure. Objective:To systematically identify causes of death associated with PM2.5 pollution and estimate the burden of death for each cause in the United States. Design, Setting, and Participants:In a cohort study of US veterans followed up between 2006 and 2016, ensemble modeling was used to identify and characterize morphology of the association between PM2.5 and causes of death. Burden of death associated with PM2.5 exposure in the contiguous United States and for each state was then estimated by application of estimated risk functions to county-level PM2.5 estimates from the US Environmental Protection Agency and cause-specific death rate data from the Centers for Disease Control and Prevention. Main Outcomes and Measures:Nonlinear exposure-response functions of the association between PM2.5 and causes of death and burden of death associated with PM2.5. Exposures:Annual mean PM2.5 levels. Results:A cohort of 4?522?160 US veterans (4?243?462 [93.8%] male; median [interquartile range] age, 64.1 [55.7-75.5] years; 3?702?942 [82.0%] white, 667?550 [14.8%] black, and 145?593 [3.2%] other race) was followed up for a median (interquartile range) of 10.0 (6.8-10.2) years. In the contiguous United States, PM2.5 exposure was associated with excess burden of death due to cardiovascular disease (56?070.1 deaths [95% uncertainty interval {UI}, 51?940.2-60?318.3 deaths]), cerebrovascular disease (40?466.1 deaths [95% UI, 21?770.1-46?487.9 deaths]), chronic kidney disease (7175.2 deaths [95% UI, 5910.2-8371.9 deaths]), chronic obstructive pulmonary disease (645.7 deaths [95% UI, 300.2-2490.9 deaths]), dementia (19?851.5 deaths [95% UI, 14?420.6-31?621.4 deaths]), type 2 diabetes (501.3 deaths [95% UI, 447.5-561.1 deaths]), hypertension (30?696.9 deaths [95% UI, 27?518.1-33?881.9 deaths]), lung cancer (17?545.3 deaths [95% UI, 15?055.3-20?464.5 deaths]), and pneumonia (8854.9 deaths [95% UI, 7696.2-10?710.6 deaths]). Burden exhibited substantial geographic variation. Estimated burden of death due to nonaccidental causes was 197?905.1 deaths (95% UI, 183?463.3-213?644.9 deaths); mean age-standardized death rates (per 100?000) due to nonaccidental causes were higher among black individuals (55.2 [95% UI, 50.5-60.6]) than nonblack individuals (51.0 [95% UI, 46.4-56.1]) and higher among those living in counties with high (65.3 [95% UI, 56.2-75.4]) vs low (46.1 [95% UI, 42.3-50.4]) socioeconomic deprivation; 99.0% of the burden of death due to nonaccidental causes was associated with PM2.5 levels below standards set by the US Environmental Protection Agency. Conclusions and Relevance:In this study, 9 causes of death were associated with PM2.5 exposure. The burden of death associated with PM2.5 was disproportionally borne by black individuals and socioeconomically disadvantaged communities. Effort toward cleaner air might reduce the burden of PM2.5-associated deaths.