Increased heat-related mortality is projected to be among the major impacts of climate change on human health, and the United States urban Northeast region is likely to be particularly vulnerable. In support of regional adaptation planning, quantitative information is needed on potential future health responses at the urban and regional scales. Here, we present future projections of heat-related mortality in Boston, New York and Philadelphia utilizing downscaled next-generation climate models and Representative Concentration Pathways (RCPs) developed in support of the Intergovernmental Panel on Climate Change (IPCC)'s Fifth Assessment Report (AR5). Our analyses reveal that heat-related mortality rates per 100,000 of population during the baseline period between 1985 and 2006 were highest in Philadelphia followed by New York City and Boston. However, projected heat-related mortality rates in the 2020s, 2050s and 2080s were highest in New York City followed by Philadelphia and Boston. This study may be of value in developing strategies for reducing the future impacts of heat and building climate change resilience in the urban Northeast region.