CLC (chemical looping combustion) promises to be a more efficient way of CO2 capture than conventional oxy-fuel combustion or post-combustion absorption. While much work has been done on CLC in the past two decades, the issue of multi-fuel compatibility has not been addressed sufficiently, especially with regard to plant layout and reactor design. In the present work, it is shown that this is non-trivial in the case of a CLC-based power plant. The underlying factors have been examined in depth and design criteria for fuel compatibility have been formulated. Based on these, a layout has been developed for a power plant which can run with either natural gas or syngas without requiring equipment changes either on the steam side or on the furnace side. The layout accounts for the higher CO2 compression costs associated with the use of syngas in place of natural gas. The ideal thermodynamic cycle efficiency, after accounting for the energy penalty of CO2 compression, is 43.11% and 41.08%, when a supercritical steam cycle is used with natural gas and syngas, respectively. It is shown that fuel switching can be enabled by incorporating the compatibility conditions at the design stage itself. © 2014 Elsevier Ltd.