BACKGROUND: Excessive summer heat is a serious environmental health problem in several European cities. Heat-related mortality and morbidity is likely to increase under climate change scenarios without adequate prevention based on locally relevant evidence. METHODS: We modelled the urban climate of Antwerp for the summer season during the period 1986-2015, and projected summer daily temperatures for two periods, one in the near (2026-2045) and one in the far future (2081-2100), under the Representative Concentration Pathway (RCP) 8.5. We then analysed the relationship between temperature and mortality, as well as with hospital admissions for the period 2009-2013, and estimated the projected mortality in the near future and far future periods under changing climate and population, assuming alternatively no acclimatization and acclimatization based on a constant threshold percentile temperature. RESULTS: During the sample period 2009-2013 we observed an increase in daily mortality from a maximum daily temperature of 26°C, or the 89th percentile of the maximum daily temperature series. The annual average heat-related mortality in this period was 13.4 persons (95% CI: 3.8-23.4). No effect of heat was observed in the case of hospital admissions due to cardiorespiratory causes. Under a no acclimatization scenario, annual average heat-related mortality is multiplied by a factor of 1.7 in the near future (24.1deaths/year CI 95%: 6.78-41.94) and by a factor of 4.5 in the far future (60.38deaths/year CI 95%: 17.00-105.11). Under a heat acclimatization scenario, mortality does not increase significantly in the near or in the far future. CONCLUSION: These results highlight the importance of a long-term perspective in the public health prevention of heat exposure, particularly in the context of a changing climate, and the calibration of existing prevention activities in light of locally relevant evidence. ; The research leading to these results has received funding from the European Community's Seventh Framework Programme ...