To better prioritise adaptation strategies to a changing climate that are currently being developed, there is a need for quantitative regional level assessments that are systematic and comparable across multiple weather hazards. This study presents an indicator-based impact assessment framework at NUTS-2 level for the European Union that quantifies potential regional changes in weather-related hazards: heat stress in relation to human health, river flood risk, and forest fire risk. This is done by comparing the current (baseline) situation with two future time periods, 2011-2040 and 2041-2070. The indicator values for the baseline period are validated against observed impact data. For each hazard, the method integrates outcomes of a set of coherent high-resolution regional climate models from the ENSEMBLES project based on the SRES A1B emission scenario, with current and projected non-climatic drivers of risk, such as land use and socio-economic change. An index of regional adaptive capacity has been developed and compared with overall hazard impact in order to identify the potentially most vulnerable regions in Europe. The results show strongest increases in impacts for heat stress, followed by forest fire risk, while for flood risk the sign and magnitude of change vary across regions. A major difference with previous studies is that heat stress risk could increase most in central Europe, which is due to the ageing population there. An overall assessment combining the three hazards shows a clear trend towards increasing impact from climaterelated natural hazards for most parts of Europe, but hotspot regions are found in eastern and southern Europe due to their low adaptive capacities. This spatially explicit assessment can serve as a basis for discussing climate adaptation mainstreaming, and priorities for regional development in the EU. © 2012 Elsevier Ltd.