The purpose of the present research was to optimize the formulation of Orodispersible tablets of Stavudine. Orodispersible tablets of Stavudine were prepared by direct compression method using different types of Superdisintegrant (Sodium Starch Glycolate, Crospovidone, Croscarmellose, and kollidan CLM) at different concentrations. The formulations were evaluated for effect of Superdisintegrant on Tablet weight variation, content uniformity, hardness, friability, wetting time, dispersion time, drug content and in vitro release also have been studied. All formulations showed satisfactory mechanical strength and tablet containing Kollidon CLM (20%) showed excellent in vitro dispersion time and drug release as compared to other formulation. The results revealed that the tablets containing 20% kollidan CLM (F20) showed short dispersion time (18 sec) with maximum drug release (100%) in 10 min. FTIR & DSC results showed no evidence of interaction between the drug and polymers. This study helps in revealing the effect of formulation processing variables on tablet properties. It can be concluded that the Orodispersible tablets of Stavudine tablets could be prepared by direct compression using kollidon CLM superdisintegrant