During the second half of the twentieth century, rapid demographic growth and urban expansion led to the development of the Mexico City metropolitan area (MCMA) urban heat island (UHI). The thermal gradient between rural and urban regions is used to define the UHI in the transition zone along the 268C isotherm of mean maximum temperature. As the MCMA expands, more natural vegetation is replaced with urbanization, and the spatial extent of the 268C isotherm grows. The loss of natural vegetation, in a densely populated region of Mexico, leads to the formation of a canopy-layer UHI. The intensification of the MCMA UHI results in an increase in the frequency of daily maximum temperatures above 308C (above 268C on a weekly average), a threshold value that constitutes a natural hazard. Warm-spell occurrences are related to an increase in the number of acute diarrhea diseases (ADD), mainly in zones of the MCMA where the socioeconomic and environmental conditions are low (e.g., insufficient access to potable water). Vulnerable people are mostly located in new settlements along the periphery of the MCMA, where large numbers of hospital discharges due to ADD are reported. The combined effect of more frequent warm spells and increasing vulnerability results in higher levels of risk of suffering this type of health problem, mainly during the warmest part of the year. This analysis may serve to develop UHI mitigation strategies and early warning systems to manage high levels of ADD risk during warm spells.