Multi-component liquid-fluidized beds are encountered in a variety of industrial processes. Often, segregation severely affects the performance of the process unit. Unfortunately, size-driven and density-driven separation processes may occur with a complex interplay, showing prevailing mechanisms that change with the operating conditions. For example, when the solids exhibit contrasting differences in size and density, even the direction of segregation can turn out hard to predict, giving rise for some systems to the so-called “layer inversion phenomenon”. A systematic experimental investigation is presented on 14 different binary beds composed of glass beads and ABS spheres with different size and density ratios and different bed composition. The analysis allows assessing the reliability of a model for predicting the segregation direction of fluidized binary beds (the Particle Segregation Model, PSM). By measurements of the solids’ concentration at the surface, expansion/segregation properties and the inversion voidage are compared with the PSM predictions, offering a direct means of model validation. Both the segregation direction throughout the expansion range and the value of the inversion voidage are compared. Extensive qualitative agreement is obtained for 12 out of 14 fluidized mixtures. Quantitatively, the average discrepancy between predicted and measured inversion voidage is below 5%, with a maximum of 17%.