Abstract From experiments, the influence of the physical characteristics of different binary mixtures of solids on the spouting regime of a pyramidal square-based spouted bed reactor is assessed. The applied methodology permits a more precise evaluation of the effects of the tested variables (diameter, density, sphericity) on the response variables (minimum air flows at which spouting begins and at which to maintain spouting conditions). The associated pressure drops along the bed of particles and the height of the formed fountain are analysed in each case. During the initial stages of fluidisation, binary mixtures containing different density ratios show dead zones. Segregation becomes more evident at large-size and high-density ratios. The lack of sphericity was found to be the main reason leading to blocking, channelling, and start-up problems when system failures occur. Nevertheless, the extent of segregation in all cases decreases with increasing the spouting velocity. In addition, a computational fluid dynamic model based on the discrete element method, previously validated for a single solid bed, is proposed as a tool to predict and evaluate potential segregation phenomena in binary mixtures. This model reproduced with high accuracy the encountered segregation phenomena. Its use may help define the technical limits inherent in the pyramidal spouted bed reactor.