Background: High temperatures have substantial impacts on mortality and, with growing concerns about climate change, numerous studies have developed projections of future heat-related deaths around the world. Projections of temperature-related mortality are often limited by insufficient information necessary to formulate hypotheses about population sensitivity to high temperatures and future demographics.Objectives: This study has derived projections of temperature-related mortality in New York City by taking into account future patterns of adaptation or demographic change, both of which can have profound influences on future health burdens.Methods: We adopt a novel approach to modeling heat adaptation by incorporating an analysis of the observed population response to heat in New York City over the course of eight decades. This approach projects heat-related mortality until the end of the 21st century based on observed trends in adaptation over a substantial portion of the 20th century. In addition, we incorporate a range of new scenarios for population change until the end of the 21st century. We then estimate future heat-related deaths in New York City by combining the changing temperature-mortality relationship and population scenarios with downscaled temperature projections from the 33 global climate models (GCMs) and two Representative Concentration Pathways (RCPs).Results: The median number of projected annual heat-related deaths across the 33 GCMs varied greatly by RCP and adaptation and population change scenario, ranging from 167 to 3331 in the 2080s compared to 638 heat-related deaths annually between 2000 and 2006.Conclusions: These findings provide a more complete picture of the range of potential future heat-related mortality risks across the 21st century in New York, and highlight the importance of both demographic change and adaptation responses in modifying future risks.