For the past few decades, there has been a considerable research interest in the area of biodegradable polymeric micro- and nanoparticles for tissue engineering, regenerative medicine, implants, stents, medical devices, and drug delivery systems. Poly(D,L-lactide-co-glycolide) (PLGA) is well-known by its safety in biomedical preparations which has been approved for human use by the FDA. The goal of this study was to evaluate the influence of process parameters on size characteristics of PLGA microparticles prepared by oil in oil (o/o) solvent evaporation technique. This method has been introduced as one of the most appropriate methods for hydrophilic agents. Scanning electron microscopy showed that prepared particles were spherical with smooth surface without aggregation. Particle size varied from 570 nm to 29 mu m in different experimental conditions. Stirring speed, polymer concentration, impeller type, and dropping size had a significant effect on the particle size. The polydispersity index of particles showed a strong relationship with the surfactant concentration, impeller type, and dropping size. It was concluded that increasing in temperature up to 50 degrees C or changing in dropping rate has a little effect on reducing the size of PLGA particles. The residual solvent content in the final suspension was less than 0.1 ppm that is in appropriate range for biomedical application. (C) 2009 Wiley Periodicals, Inc. I Appl Polym Sci 116: 528-534, 2010