Over the last few decades, heat waves have intensified and have led to excess mortality. While the probability of being affected by heat stress has significantly increased, the risk of heat mortality is rarely quantified. This quantification of heat mortality risk is necessary for systematic adaptation measures. Furthermore, heat mortality records are sparse and short, which presents a challenge for assessing heat mortality risk for future climate projections. It is therefore crucial to derive indicators for a systematic heat mortality risk assessment. Here, risk indicators based on temperature and mortality data are developed and applied tomajor cities in Germany, France, and Spain using regional climatemodel simulations. Biascorrected dailymaximum, minimum, and wet-bulb temperatures show increasing trends in future climate projections for most considered cities. In addition, we derive a relationship between daily maximum temperatures and mortality for producing future projections of heatmortality risk fromextreme temperatures that is based on low(representative concentration pathway RCP2.6) and high (RCP8.5) emission scenario future climate projections. Our results illustrate that heatmortality increases by about 0.9% decade(-1) in Germany, 1.7% decade(-1) in France, and 7.9% decade(-1) in Spain for RCP8.5 by 2050. The future climate projections also show that wet-bulb temperatures above 30 degrees C will be reached regularly, withmaxima above 40 degrees C likely by 2050. Our results suggest a significant increase of heat mortality in the future, especially in Spain. On average, our results indicate that themortality risk trend is almost 2 times as high in all three countries for the RCP8.5 scenario relative to RCP2.6. SIGNIFICANCE STATEMENT: Anthropogenic greenhouse gas emissions have led to an increase in temperatures over the last century. This general warming leads to more intensive and more frequent heat waves that affect humans adversely. Extreme temperatures exert heat stress on the human body and can lead to reduced productivity, sickness, and death. Herewe derive a statistical relationship between extreme temperatures and the number of deaths inmajor cities in three European countries so as to be able to use future climate simulations to determine likely numbers of heat-related deaths. Our results show that the number of heat-related deaths will increase in major European cities by 2050 and will be 2 times as high for high greenhouse gas emissions simulations as for low greenhouse gas emissions simulations.