This work reports the immobilization of Fenbufen, a nonsteroidal anti-inflammatory drug, into two different hexagonal mesoporous silicas (MCM-41) which exhibit some differences in terms of morphology and pore size, and their behavior as systems for sustained release at pH 7.5. The drug/mesoporous silica systems have been characterized by powder X-ray diffractometry (PXRD), Fourier transform infrared spectroscopy (FT-IR), N(2) adsorption-desorption, and transmission electron microscopy (TEM). The results show that the drug is mainly incorporated inside the pores, and its loading is dependent on both the pore size and the impregnation temperature. The Fenbufen/mesoporous-silica systems give a well-sustained release profile, releasing 100% of the initially loaded drug at the end of the in vitro assays.