On April 2009, a three-year-project was launched within the 7th Framework Programme (FP) of the European Commission: the Central Design Team (CDT) for a FAst Spectrum Transmutation Experimental Facility (FASTEF). CDT had the objective to define a preliminary design of the MYRRHA reactor. In addition to being a multi-purpose irradiation facility, MYRRHA should beable to demonstrate the Acceleration Driven System concept at ∼100 MW power level and an efficient transmutation of minor actinides, as main contributors to high-level long-lived radioactive wastes. This paper describes the design of cores able to operate the MYRRHA-FASTEF plant in both critical andsub-critical modes. The design studies were performed by detailed neutronic analyses (with determinis-tic and Monte Carlo methods) and by accurate thermal-hydraulic evaluations (at the fuel assembly andpin sub-channel level), by taking also into account thermo-mechanical and safety constraints. Among themost significant core features, the fast flux level (>0.75 MeV∼ 1015cm−2s−1), the high flexibility for irradi-ation purposes and the limited overall dimension (impacting on the cost of the plant) can be noticed. Thetransmutation of minor actinides, enhanced by the high fast flux, reaches values of about 32 kgHMTWh−1in both operational modes.