The objective of the present study is to develop and characterize floating microspheres of Stavudine, which after oral administration could prolong the gastric residence time and increase the bioavailability of the drug, in order to provide the sustained release to minimize the dose dependent side effects as well as to improve patient compliance. Stavudine microspheres were prepared by solvent evaporation method using combination of Ethyl cellulose (EC) and Di butyl Phthalate (DB) as polymer in different ratios. The prepared microspheres were evaluated for micrometric properties, encapsulation efficiency, particle size analysis, surface morphology, in-vitro drug release and stability studies. The shape and surface morphology of the microspheres were characterized by optical and scanning electron microscopy. The resultant microspheres were discrete and free flowing. Mean particle size of microspheres was in range of 222-253 μm for different formulations. The encapsulation efficiency was in range of 48-58.5% and found to be dependent upon the polymer concentration with highest encapsulation was obtained in case of EC:DB with ratio 1:1. The FTIR and DSC confirmed the stable character of stavudine in drug-loaded microspheres with no drug polymer interaction. The in-vitro drug release data was fitted into various kinetic models in order to find out the release mechanism. The in vitro studies revealed the controlled release of drug from microspheres up to 12 h while still remained buoyant.