In recent papers we have discussed the use of cuboid packed-bed devices as alternative to columns for chromatographic separations. These devices address some of the major flow distribution challenges faced by preparative columns used for process-scale purification of biologicals. Our previous studies showed that significant improvements in separation metrics such as the number of theoretical plates, peak shape, and peak resolution in multi-protein separation could be achieved. However, the length-to-width aspect ratio of a cuboid packed-bed device could potentially affect its performance. A systematic comparison of six cuboid packed-bed devices having different length-to-width aspect ratios showed that it had a significant effect on separation performance. The number of theoretical plates per meter in the best-performing cuboid packed-bed device was about 4.5 times higher than that in its equivalent commercial column. On the other hand, the corresponding number in the worst-performing cuboid-packed bed was lower than that in the column. A head-to-head comparison of the best-performing cuboid packed bed and its equivalent column was carried out. Performance metrics compared included the widths and dispersion indices of flow-through and eluted protein peaks. The optimized cuboid packed-bed device significantly outperformed its equivalent column with regards to all these attributes.