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In 1997 the U.S. Environmental Protection Agency set the first annual National Ambient Air Quality Standard (NAAQS) for fine particulate matter (PM2.5). Although the weight of scientific evidence has determined that a causal relationship exists between PM2.5 exposures and cardiovascular effects, few studies have concluded whether NAAQS-related reductions in PM2.5 led to improvements in public health.We examined the change in cardiovascular (CV) mortality rate and the association between change in PM2.5 and change in CV-mortality rate before (2000–2004) and after implementation of the 1997 annual PM2.5 NAAQS (2005–2010) among U.S. counties. We further examined how the association varied with respect to two factors related to NAAQS compliance: attainment status and design values (DV). We used difference-in-differences and linear regression models, adjusted for sociodemographic confounders.Across 619 counties, there were 1.10 (95% CI: 0.37, 1.82) fewer CV-deaths per year per 100,000 people for each 1 μg/m3 decrease in PM2.5. Nonattainment counties had a twofold larger reduction in mean annual PM2.5, 2.1 μg/m3, compared to attainment counties, 0.97 μg/m3. CV-mortality rate decreased by 0.59 (95% CI: −0.54, 1.71) in nonattainment and 1.96 (95% CI: 0.77, 3.15) deaths per 100,000 people for each 1 μg/m3 decrease in PM2.5 in attainment counties. When stratifying counties by DV, results were similar: counties with DV greater than 15 μg/m3 experienced the greatest decrease in mean annual PM2.5 (2.29 μg/m3) but the smallest decrease in CV-mortality rate per unit decrease in PM2.5, 0.73 (95% CI: −0.57, 2.02).We report a significant association between the change in PM2.5 and the change in CV-mortality rate before and after the implementation of NAAQS and note that the health benefits per 1 μg/m3 decrease in PM2.5 persist at levels below the current national standard.US EPA intermural research.PM2.5 decreased following implementation of annual PM2.5 standard.Cardiovascular mortality decreased with a decrease in PM2.5.Attainment counties had greater health benefit compared to nonattainment counties.Associations were not statistically different.Health benefits were shown even in counties below the current standard.