Abstract Safety studies are performed in the frame of the conceptual design studies for the European Demonstration Fusion Power Plant (DEMO) to assess the safety and environmental impact of design options. An exhaustive set of reference accident sequences are defined in order to evaluate plant response in the most challenging events and compliance with safety requirements. The Functional Failure Mode and Effect Analysis (FFMEA) has been chosen as analytical tool, as it is a suitable methodology to define possible accident initiators when insufficient design detail is available to allow for more specific evaluation at component level. The main process, safety and protection functions related to the DEMO plant are defined through a functional breakdown structure (FBS). Then, an exhaustive set of high level accident initiators is defined referring to loss of functions, rather than to specific failures of systems and components, overcoming the lack of detailed design information. Nonetheless reference to systems or main components is always highlighted, as much as possible, in order to point out causes and safety consequences. Through the FFMEA a complete list of postulated initiating events (PIEs) is selected as the most representative events in terms of challenging conditions for the plant safety. All the four blanket concepts of the European DEMO reactor have been analysed.