In this work, a spraying technique was used to encapsulate etanidazole (a hypoxic radiosensitizer) into different poly(lactide/glycolide) polymers. The properties of the obtained microspheres, especially the particle size and distribution, morphology and release rate were investigated. Unexpectedly, poly(L-lactide) (PLLA) shows a fast release rate, comparable to PLGA 50: 50, due to the dissociation of the microspheres although the release rate of the spray-dried microspheres of other polymers decreases with increasing lactide ratio. It is also interesting to note that, contrary to the viscosity sequence of the polymer solutions, the particle size of the microspheres decreases in the order PLGA 50: 50, PLGA 65: 35, PLGA 85: 15 and PDLA. The morphology of microspheres can be affected by polymer properties (e.g. lactide/glycolide ratio, molecular weight, crystallinity and Tg) and fabrication conditions (e.g. solvent and polymer concentration to be sprayed). Although most of the microspheres fabricated by EA have a donghnut-like shape with smooth surface, it is possible to obtain spherical particles by choosing proper polymer type and polymer concentration. A further examination of the mechanisms of the atomization process and the solvent evaporation process reveals their respective effect on droplet formation and particle formation, both of which are essential for the spray-drying technique. It is found that polymer phase transition (affected by the polymer solubility) and its subsequent solvent evaporation processes can finally determine the morphology and the particle size of the spray-dried particles made from different polymers. In essence, the lactide/glycolide ratio of the polymers plays a more important role in affecting the properties of the spray-dried microspheres.