The purpose of this study was to investigate the influences of drying methods on the risperidone (RIS) release profiles of RIS-loaded PLGA microspheres. These microspheres were fabricated with an O/W emulsion solvent evaporation method. The wet microspheres were dried with freeze drying and vacuum drying methods. The microspheres were mono-dispersed spheres with an average diameter of 100m. Studies found that drying methods had great influence on the porosity, morphology, and release profiles of RIS-loaded PLGA microspheres. Specifically, the freeze-dried microspheres had higher porosity (78.46 +/- 1.64%) than those vacuum-dried ones (52.45 +/- 2.68%), and they showed higher RIS release rates (p<0.05). In the accelerated release tests (45 degrees C), these microspheres dried under the pressures of 700mmHg and 200mmHg gave faster release rates than those ones dried under the pressure of 450mmHg. Importantly, the accelerated release test (45 degrees C) had a high correlation with the real-time test (37 degrees C) (R-2>0.99). These studies exhibited a significance in the precise preparation of RIS-loaded PLGA microspheres.