I present the results of studies from two historically separate fields of research: heat related illness and human thermal comfort adaptation. My research objectives were: (a) to analyze the relationships between climate and heat related morbidity in Phoenix, Arizona and Chicago, Illinois; (b) explore possible linkages of human thermal comfort adaptation to heat-related illness; and (c) show possible benefits of collaboration between the two fields of research. Previous climate and mortality studies discovered regional patterns in summertime mortality in North America: lower in hot, southern cities compared to more temperate cities. I examined heat related emergency (911) dispatches from these two geographically and climatically different cities. I analyzed with local weather conditions with 911 dispatches identified by responders as "heat" related from 2001 to 2006 in Phoenix and 2003 through 2006 in Chicago. Both cities experienced a rapid rise in heat-related dispatches with increasing temperature and heat index, but at higher thresholds in Phoenix. Overall, Phoenix had almost two and half times more heat-related dispatches than Chicago. However, Phoenix did not experience the large spikes of heat-related dispatches that occurred in Chicago. These findings suggest a resilience to heat-related illness that may be linked to acclimatization in Phoenix. I also present results from a survey based outdoor human thermal comfort field study in Phoenix to assess levels of local acclimatization. Previous research in outdoor human thermal comfort in hot humid and temperate climates used similar survey-based methodologies and found higher levels of thermal comfort (adaptation to heat) that in warmer climates than in cooler climates. The study presented in this dissertation found outdoor thermal comfort thresholds and heat tolerance levels in Phoenix were higher than previous studies from temperate climates more similar to Chicago. These differences were then compared to the differences in weather conditions associated with heat-related dispatches. The higher comfort thresholds in Phoenix were similar in scale to the climate differences associated with the upsurge in heat-related dispatches in Phoenix and Chicago. This suggests a link between heat related illness and acclimatization, and illustrates potential for collaboration in research between the two fields.