Background - Air pollution is a major environmental health concern in France and around the world. Numerous toxicological and epidemiological studies highlight the many harmful effects of outdoor air pollution on health. A quantitative health impact assessment (EQIS) of ambient air pollution was conducted in the Auvergne-Rhône-Alpes region to enable local stakeholders to measure the potential benefits of improved air quality on mortality and various health indicators within their territory. Method - To estimate the average population exposure to air pollution in all municipalities of the region, concentrations of fine particulate matter with a diameter of less than 2.5 µm (PM2.5) and nitrogen dioxide (NO2: a tracer pollutant for traffic-related pollution) derived from fine-scale modeling (2016–2018) were linked to population data. The impact of these pollutants was assessed by considering the following health outcomes: deaths, hospitalizations for stroke, incidence of lung cancer, and emergency department visits for asthma in children. Results - Each year in Auvergne-Rhône-Alpes, nearly 4,300 deaths are estimated to be attributable to population exposure to PM2.5 and 2,000 deaths to population exposure to NO2, representing 7% and 3% of total annual mortality, respectively. However, these two figures cannot be added together because some of the deaths may be attributable to combined exposure to both pollutants. This study also estimates that nearly 200 lung cancers, 780 strokes, and 550 emergency room visits for asthma in children are attributable to exposure to PM2.5. Conclusion - These results confirm the significant impact of ambient air pollution on the health of the region’s population and underscore the importance of strengthening efforts to improve air quality, particularly at the local level.