Climate change may increase the frequency and intensity of ozone episodes in future summers in the United States. However, only recently have models become available that can assess the impact of climate change on O3 concentrations and health effects at regional and local scales that are relevant to adaptive planning. We developed and applied an integrated modeling framework to assess potential O3-related health impacts in future decades under a changing climate. The National Aeronautics and Space Administration-Goddard Institute for Space Studies global climate model at 4 degrees x 5 degrees resolution was linked to the Penn State/National Center for Atmospheric Research Mesoscale Model 5 and the Community Multiscale Air Quality atmospheric chemistry model at 36 km horizontal grid resolution to simulate hourly regional meteorology and O3 in five summers of the 2050s decade across the 31-county New York metropolitan region. We assessed changes in O3-related impacts on summer mortality resulting from climate change alone and with climate change superimposed on changes in O3 precursor emissions and population growth. Considering climate change alone, there was a median 4.5% increase in O3-related acute mortality across the 31 counties. Incorporating O3 precursor emission increases along with climate change yielded similar results. When population growth was factored into the projections, absolute impacts increased substantially. Counties with the highest percent increases in projected O3 mortality spread beyond the urban core into less densely populated suburban counties. This modeling framework provides a potentially useful new tool for assessing the health risks of climate change.