The health impact assessment (HIA) of air pollution in the Avignon metropolitan area is consistent with the guidelines of the Provence-Alpes-Côte d'Azur Regional Air Quality Plan, which aims to prevent, reduce, or mitigate the effects of air pollution. In this study, the short-term health impact of air pollution is calculated in terms of morbidity (hospital admissions) and premature mortality. The long-term health impact is estimated based on the number of deaths attributable to air pollution. The study area selected corresponds to an urban zone where the population’s exposure to air pollution can be considered homogeneous. It comprises seven municipalities: five in Vaucluse (Avignon, Le Pontet, Morières-les-Avignon, Sorgues, and Vedène) and two in Gard (Les Angles and Villeneuve-les-Avignon), representing a total population of 153,624 inhabitants. Two study periods were defined: the 1999–2000 period for short- and long-term assessments of mortality, and the year 2001 for the analysis of morbidity. This study is based on the methodological principles of the Urban Air Pollution Health Impact Assessment (EIS), whose methodology consists of four steps: hazard identification, exposure estimation, selection of exposure-risk relationships, and risk characterization. The pollution indicators selected are based on the four pollutants routinely measured in the area: NO2, O3, PM10, and SO2. The exposure-risk relationships used are derived from epidemiological studies conducted in the general population, with a focus on multicenter and European studies. The annual number of premature deaths attributable to air pollution is 23, including 10 deaths from cardiovascular causes and 2 deaths from respiratory causes. The calculation of health benefits, associated with various air pollution reduction scenarios, shows that the most effective scenarios are those corresponding to 25% reductions in the annual average of the pollutant in question. Regarding long-term health benefits, the various scenarios show that the European standard set for 2005 is already being met. Compliance with the European standard set for 2010 is expected to prevent 10 deaths out of the total number of deaths recorded in a year, whereas a 25% reduction in the annual average would prevent 25. Given the uncertainties and limitations of the methodology used, the results should be interpreted as orders of magnitude of the impact of air pollution on the health of the population in the study area. However, this study shows that, even though the relative risks associated with air pollution are low, the large proportion of people exposed results in a significant collective impact on mortality. It also shows that health effects already appear at pollution levels well below those for which measures are currently taken, and that the most effective actions would therefore be those that combine daily reductions in emissions at the source with a significant decrease in the number of annual pollution peaks.