Mesoporous silicon microparticles with three various surface chemistries and eight different average pore diameters for each surface modification, ranging from 11 to 75 nm, were loaded with ibuprofen. The loaded batches were characterized using thermal analysis and nitrogen sorption. Three thermodynamically different states of ibuprofen were found in the samples: a crystalline state outside the pores, a crystalline state inside the pores, and a disordered state inside the pores. Both the crystalline and disordered ibuprofen were found in the pores in all of the batches. Crystalline ibuprofen outside the pores was only found in two batches and in negligible amounts. The results supported the assumption that there is a layer of disordered ibuprofen adjacent to the pore wall (i.e., delta layer), in which the thickness is not strongly depending upon the pore size. The thickness of the disordered layer varied depending upon the surface chemistry of the pore wall and was 1.2, 1.5, and 2.0 nm for hydrogen-terminated, thermally oxidized, and thermally carbonized surfaces, respectively. The method gave detailed information on the physical state of ibuprofen in the batches. It can be used with any drug compound that is able to form crystals inside the mesopores and can be a useful tool in determining the optimal surface chemistry and pore size of a mesoporous drug-carrier material.