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The use of low-NOx compressed natural gas (CNG) medium-duty vehicles (MDVs) and heavy-duty vehicles (HDVs) has the potential to significantly reduce NOx emissions and yield improvements in regional air quality. However, the extent of air quality improvement depends on many factors including future levels of vehicle deployment, the evolution of emissions from other sources, and meteorology. An analysis of the impacts requires modeling the atmosphere to account for both primary and secondary air pollutants, and the use of health impact assessment tools to map air quality changes into quantifiable metrics of human health. Here, we quantify and compare the air quality and health impacts associated with the deployment of low-NOx CNG engines to power future MDV and HDV fleets in California relative to both a business-as-usual and a more advanced fleet composition. The results project that reductions in summer ground-level ozone could reach 13 ppb when compared to a baseline fleet of diesel and gasoline HDV and MDV and could reach 6 ppb when compared to a cleaner fleet that includes some zero-emission vehicles and fuels. Similarly, for all CNG cases considered reductions in PM2.5 are predicted to range from 1.2 ug/m3 to 2.7 ug/m3 for a summer episode and from 3.1 ug/m3 to approximately 7.8 ug/m3 for a winter episode. These improvements yield short-term health benefits equivalent to $47 to $56 million in summer and $38 to $43 million in winter during episodes conducive to poor air quality. Additionally, the use of zero emission vehicle options such as battery electric and hydrogen fuel cell trucks could achieve approximately 25% to 31% higher benefits for an equivalent fleet penetration level due to the additional emission reductions achieved. Implications: The paper provides a quantitative estimate of the air quality and human health benefits that can be achieved through the use of novel compressed natural gas engines (i.e., low-NOx CNG) in medium- and heavy-duty vehicles and provide a comparison with zero emission vehicles. Thus, our findings will provide support for policy development seeking to transform the trucking sector to meet clean air and climate goals given the current struggle policymakers have with selecting between alternative truck technologies due to variance in factors like cost and technical maturity. [ABSTRACT FROM AUTHOR]