The U.S. Environmental Protection Agency (U.S.EPA) recently promulgated regulations to reduce air pollution from heavy-duty vehicles. This article reports the estimated health benefits of reductions in ambient particulate matter (PM) concentrations associated with those regulations based on the best available methods of benefits analysis. The results suggest that when heavy-duty vehicle emission reductions from the regulation are fully realized in 2030, they will result in substantial, broad scale reductions in ambient particulate matter. This will reduce the incidence of premature mortality by 8,300, chronic bronchitis by 5,500, and respiratory and cardiovascular hospital admissions by 7,500. In addition, over 175,000 asthma attacks and millions of respiratory symptoms will be avoided in 2030. The economic value of these health benefits is estimated at over $65 billion.