A comprehensive study of aspirin loading and release from MCM-41 and amine functionalized MCM-41 was conducted. Two different functionalization methods, co-condensation and postsynthesis modification, were utilized and compared. All of the MCM-41 samples were thoroughly characterized before and after aspirin loading by powder X-ray diffraction, nitrogen adsorption isotherms, and thermogravimetric analysis to determine the structure and physicochemical properties such as surface area, pore volume, and functional group loading. Molecular level details about the aspirin−MCM-41 interactions were revealed through FTIR and 13 C solidstate NMR experiments. For the aminopropyl-functionalized MCM-41, the carboxylic acid group of aspirin associates with the amine group of the functionalized MCM-41. In all of the samples, an interaction between the aspirin phenyl group and the mesoporous silica host was hypothesized based on shifts in the phenyl group 13 C NMR resonances. Molecular dynamics simulations supported the NMR observations in that the phenyl group of the aspirin was determined to be oriented parallel to the pore wall. The release data indicated that both the distribution and loading of the amine functional groups in MCM-41 influenced the release properties of aspirin.