The exploration of a method to tailor a biodegradable polymer into microparticles/nanoparticles with a desirable morphology and size may result in their enhanced performance as biomedical devices for drug delivery and simplify the preparation process. A modified electrohydrodynamic liquid atomization (EHDA) process is reported here for the preparation of poly(lactic-co-glycolic acid) (PLGA) microparticles. To understand systematically the EHDA method for the preparation of PLGA microparticles, PLGAs of four different molecular weights were electrosprayed under different conditions involving changes in the applied potential, liquid flow rate, polymer concentration, and solvent. The results show that the right concentration range of PLGA is key for electrospraying the spherical particles. A solution with a low-molecular-weight PLGA has a wider concentration range for electrospraying into spherical particles than a solution with a high-molecular weight PLGA. At the concentration at which spherical particles are formed, the diameter of the as-sprayed particles is not affected substantially by the applied potential and PLGA molecular weight, but it increases monotonically with the liquid flow rate and PLGA concentration. Experimentation further demonstrated that low electric conductivity, a low dielectric constant, and a high vapor pressure of chloroform are favorable for controlling the EHDA process solvent N,N-dimethylformamide with opposite solvent properties and, at the same time, produces smaller and poly-disperse particles. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 113: 526-534, 2009