To quantify the on-road PM -related premature mortality at a national scale, previous approaches to estimate concentrations at a 12-km × 12-km or larger grid cell resolution may not fully characterize concentration hotspots that occur near roadways and thus the areas of highest risk. Spatially resolved concentration estimates from on-road emissions to capture these hotspots may improve characterization of the associated risk, but are rarely used for estimating premature mortality. In this study, we compared the on-road PM -related premature mortality in central North Carolina with two different concentration estimation approaches-(i) using the Community Multiscale Air Quality (CMAQ) model to model concentration at a coarser resolution of a 36-km × 36-km grid resolution, and (ii) using a hybrid of a Gaussian dispersion model, CMAQ, and a space-time interpolation technique to provide annual average PM concentrations at a Census-block level (∼105,000 Census blocks). The hybrid modeling approach estimated 24% more on-road PM -related premature mortality than CMAQ. The major difference is from the primary on-road PM where the hybrid approach estimated 2.5 times more primary on-road PM -related premature mortality than CMAQ due to predicted exposure hotspots near roadways that coincide with high population areas. The results show that 72% of primary on-road PM premature mortality occurs within 1,000 m from roadways where 50% of the total population resides, highlighting the importance to characterize near-road primary PM and suggesting that previous studies may have underestimated premature mortality due to PM from traffic-related emissions.