The preparation of ketoprofen spray-dried microspheres can be affected by the long drug recrystallization time. Polymer type and drug-polymer ratio as well as manufacturing parameters affect the preparation. The purpose of this work was to evaluate the possibility to obtain ketoprofen spray-dried microspheres using the Eudragit RS and RL; the influence of the spray-drying parameters on morphology, dimension, and physical stability of microspheres was studied. Ketoprofen microspheres based on Eudragit blend can be prepared by spray-drying and the nebulization parameters do not influence significantly particle properties; nevertheless, they can be affected by drying and storage methods. No effect of the container material is found.