Spray dried mesoporous silica microspheres have the potential to be used in a vast number of applications. However, the highly ordered mesostructure is often rendered inaccessible by the presence of a thin skin on the particle formed by spray drying. Here we post-treated these silica microspheres hydrothermally to increase the pore size of the mesostructures, as well as to open up the skin. The hydrothermal treatment also improved the long-range ordering of some disordered regions that were formed due to the rapid nature of self-assembly in spray-drying, as evidenced by the SAXS patterns after treatment. Increasing the hydrothermal treatment temperature above 100. ?C increased the pore size, while surface area, wall thickness, and the micropore volume decreased as a result of the densification of the silica walls. The effect of time on the hydrothermal treatment (6-24. h) was less pronounced on the long-range ordering and pore size. Instead the treatment time had a more significant impact to reduce the micropore volume, indicating that the long-range ordering is improved within 6. h. While the densification of the pore walls and hence reduction of the micropore volume occurs at a slower rate over a period of 24. h. To compare the performance of hydrothermally treated and untreated particles, both materials were used for static and packed bed adsorption of lysozyme. The treated particles significantly out-performed (>260 capacity) the untreated particles, demonstrating a faster adsorption in the packed bed, whereas almost no adsorption was observed for the untreated material due to the barrier presented by the skin.