Abstract Without intervention, by the end of this century, extreme heat will cause tens of thousands of excess deaths. Developing a complete understanding of the long-term burden of deaths from heat, and characteristics that heighten or reduce heat vulnerability, is critical – for illuminating the urgency of climate change mitigation strategies and informing the design of interventions for heat adaptation. It is well accepted that heat vulnerability is determined by biologic susceptibility, adaptive capacity, and exposure intensity, and that most heat-related deaths - particularly among the elderly in the United States and Europe - occur indoors. Nevertheless, current understanding of heat-related mortality and vulnerability remains limited. First, most research on heat-related death has quantified acute (short-term) associations between temperature and mortality; as a result, there remains uncertainty about the long-term burden of deaths attributable to heat. Second, most research has calculated associations with outdoor rather than indoor temperatures, thus potentially misclassifying exposures and under-estimating the mortality impacts of heat. Additionally, little is known about the extent to which housing interventions that promote thermal comfort, such as improving insulation or altering roofing material, may prevent excess deaths from heat. There is an urgent need to fill these gaps, since most people, and especially heat vulnerable subpopulations like the elderly, spend the majority of their time inside. Here, we propose a longitudinal cohort study of a nationally representative sample of age 65 and older adult participants of the Mortality Disparities in America Communities (MDAC) study linked with Medicare and National Death Index data. We will combine these data with indoor temperature and humidity variables calculated using building science and physics-based simulation models; individual-level housing characteristics derived from nationally representative survey data; and high-resolution land cover data. We will leverage the resulting large, population-based database, consisting of a remarkably rich set of person- and neighborhood-level variables, to improve understanding of associations between housing characteristics, indoor temperature exposures, and mortality, and person- and neighborhood-level determinants of heat vulnerability. In Aim 1, we will quantify associations between summertime indoor temperature exposures and longer-term all-cause and cause-specific mortality. In Aim 2, we will elucidate person- and neighborhood-level factors that enhance or reduce vulnerability to indoor heat. In Aim 3, we will quantify the total excess deaths that may be prevented through housing interventions that improve thermal comfort - under current and future climate scenarios. We will stratify all analyses by climate zone and by urbanicity levels, to account for differences in urbanization-related heat exposures, built- environments, and physiol...