For the acceptability of energy systems, environmental impacts are becoming more and more important. One primary way for reducing impacts related to processes is by improving efficiency of plants. A key instrument currently used to verify such improvements is exergy analysis, extended to include also the environmental externalities generated by systems. Through exergy-based analyses, it is possible indeed to evaluate the overall amount of resources consumed along all the phases of the life cycle of a system, from construction to dismantling. However, resource consumption is a dimension of the impact of a system at global level, while it may not be considered a measure of its local impact. In the paper a complementary approach named Combined Risk and Exergy Analysis (CRExA) to assess impacts from major accidents in energy systems is proposed, based on the combination of classical exergy analysis and quantitative risk analysis (QRA). Impacts considered are focused on effects on human health. The approach leads to the identification of solutions to minimize damages of major accidents by acting on the energy system design. (C) 2013 Elsevier Ltd. All rights reserved.