A quasi-emulsion solvent diffusion method to prepare microspheres of ketoprofen with an acrylic polymer was studied. The solvent and drug concentration profiles in the continuous emulsion phase were determined experimentally under different processing conditions, in order to investigate the mechanism of microsphere formation. It was found that the solvent removal rate from the emulsion droplets as well as the microsphere size distribution, were affected by factors such as the drug-to-polymer ratio, the initial difference of temperature between the emulsion phases, and the solvent/non-solvent ratio. The results of the investigations concerning the morphology and the ketoprofen dissolution profiles, obtained from in vitro dissolution studies, are also presented. The difference in the hardening of the periphery of the emulsion droplets resulted in different drug release rates, as clearly shown by the experimental data. It was concluded that solidification and water uptake are compromising processes during microsphere formation. Depending on the cases considered, it may be the solidification or the water uptake which dominates the process.