The relationship between heat stress and mortality in the federal state of Vienna (Austria) was analyzed from 1970 to 2007. Long-term trends of mortality data and short-term adaptation to heat stress were considered by two complex approaches. The evaluation is based on the human biometeorological parameter, physiologically equivalent temperature. The results revealed a significant impact of heat stress on the human health, with a significantly higher sensitivity on women compared to men. Additionally, higher risks of deaths due to cardiovascular and respiratory diseases were found. During the long period of 38 years, some significant decreases of the sensitivity were found, especially in the medium heat stress levels. This could indicate active processes of long-term adaptation to the increasing heat stress.