Background: During the development of regional air quality plans in France, assessments of the short-term health impacts of urban air pollution were conducted using exposure-risk relationships derived from time-series studies. The World Health Organization (WHO) has suggested that exposure-risk relationships derived from cohort studies should also be taken into account to assess the impact of chronic exposure and to estimate the number of deaths attributable to air pollution. This article presents the approach implemented in Nantes to characterize the long-term impact of air pollution in terms of years of life lost, in addition to the assessment of the number of attributable deaths. Method: The study population is divided into birth cohorts. For each cohort, two survival curves are constructed based on current mortality rates. The first curve is determined using current levels of air pollution exposure, while the second is established for exposures at a lower reference level. The areas between the two survival curves represent the years of life lost attributable to urban air pollution. Results: The impact of air pollution was estimated at approximately 56 premature deaths, or about 2.0% of deaths among Nantes residents aged 30 and older. The number of years of life lost by this population was estimated at 27.2 years in 1999 and 2,388.1 years over the 1999–2008 period. The reduction in life expectancy at age 30 was estimated at approximately 0.3 years. Conclusions: After identifying and discussing errors and uncertainties, this study confirmed the existence in Nantes of a significant health impact from air pollution and reaffirmed the essential role of chronic exposure in the manifestation of this impact. The quantification of years of life lost and the reduction in life expectancy provides, within the context of local studies, new evidence to refute the hypothesis that health impacts are limited to premature deaths among individuals at the end of life. Despite moderate pollution levels, the expected health benefits in Nantes are of the same order of magnitude, or even greater, than those estimated in nine other French cities for the same reduction in exposure to air pollution.