This study deals with the production of poly(DL-lactide-co-glycolide) (PLGA) microspheres using ethyl acetate as a dispersing solvent, a partially water soluble and less toxic solvent, by using emulsification and solvent diffusion/evaporation techniques. PLGA 50 : 50 was used, having molecular weights, 12 000 and 34 000 with the end group capped (RG502, 503) and uncapped (RG502H, 503H) biodegradable polymers. The microspheres were loaded with nifedipine (NFD) as a model drug. Solvent removal from the embryonic microspheres was manipulated by adopting different techniques. These methods have shown a significant effect on the physicochemical and release characteristics of the microspheres. Rapid removal of the solvent resulted in microspheres with a loose matrix and large size. Use of higher molecular weight polymers increased the size of the microspheres as well as delayed release of the drug. The uncapped polymer has given a higher rate of diffusion when compared to the capped polymers. Thermal analyses showed a uniform molecular distribution of the drug in the polymer matrix. The mechanism of drug release from the PLGA microspheres followed the Fickian diffusion.