The Toronto–Windsor corridor of Southern Ontario, Canada, experiences hot and humid weather conditions in summer, thus exposing the population to heat stress and a greater risk of mortality. In the event of a climate change, heat-stress conditions may become more frequent and severe in Southern Ontario. To assess the impact of summer weather on health, we analyzed heat-related mortality in the elderly (older than 64 years) in the metropolitan areas of Windsor, London, Kitchener-Waterloo-Cambridge, Hamilton, and Toronto for a 17-year period. Demographic, socioeconomic, and housing factors were also evaluated to assess their effect on the potential of the population to adapt and their vulnerability to heat stress. Heat-stress days were defined as those with an apparent temperature (heat index) above 32°C. Mortality among the elderly was significantly higher on heat-stress days than on non-heat-stress days in all cities except Windsor. The strongest relationships occurred in Toronto and London, followed by Hamilton. Cities with the greatest heat-related mortality have relatively high levels of urbanization and high costs of living. Even without the warming induced by a climate change, (1) vulnerability is likely to increase as the population ages, and (2) ongoing urban development and sprawl are expected to intensify heat-stress conditions in Southern Ontario. Actions should be taken to reduce vulnerability to heat stress conditions, and to develop a comprehensive hot weather watch/warning system for the region.