The health impacts of outdoor air pollution are a major concern in the Arve Valley, where the concentration of human activities, the topography, and climatic conditions contribute to the accumulation of pollutants. A quantitative health impact assessment (EQIS) was conducted to help local stakeholders measure the expected benefits of improved air quality on mortality and life expectancy. To assess the effects of chronic exposure, annual average concentrations of fine particulate matter from a high-resolution environmental model were combined with land-use data to estimate population exposure in the municipalities covered by the air quality protection plan. The study shows that 8% of mortality in the Arve Valley is attributable to PM2.5 fine particulate matter, representing 85 deaths per year. Reducing annual average concentrations of fine particulate matter (PM2.5) by 30% would reduce mortality by 4%, equivalent to 45 deaths prevented per year, and 967 life-years gained, corresponding on average to a 5-month increase in life expectancy for the population. The qualitative analysis of uncertainties suggests that the health impacts are underestimated, as this EQIS provides a minimum order of magnitude for the impact. The impact of air pollution in the Arve Valley would thus be similar to that found in French urban areas, without reaching the levels of the most polluted major urban centers. Ultimately, this study confirms the position taken by Santé publique France in its response to the ARS’s referral in May 2015, namely that actions must be taken without delay to sustainably improve air quality in the Arve Valley.