Objectives: Stavudine has a low half-life of 0.8-1.5 hr and therefore needs recurrent administration to sustain stable beneficial drug plasma levels. In order to enhance and preserve the stable drug level of stavudine for round the clock, gastroretentive systems (floating low-density formulations that cause buoyancy on the gastric fluid in the stomach) may prove to be advantageous for releasing the drug content from the matrix tablet reservoirs for several hours. Materials and Methods: The current research endeavors towards formulating the stavudine floating tablet formulations (F1-F9) employing rate modifying polymers such as HPMC K15M, xanthan gum and HPMC K100M using multiple punch tablet compression machine containing 9 mm diameter, round flat-faced punches to form 80 mg tablet with a batch size of 100. The drug-polymer compatibility was investigated through Fourier-Transformed Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC). Results: The stavudine floating tablet formulations were successfully fabricated. The pre-compression characteristics (tapped density, bulk density, Hausner's ratio, Carr's index and angle of repose) as well as postcompression characteristics (appearance, hardness, dimension, drug content, friability, swelling index, weight variation, in vitro drug release, in vitro buoyancy, accelerated stability and drug release kinetics for 90 days) of the formulations were comprehensively studied. Conclusion: This research study on stavudine will definitely open several new milestones for anti-retroviral pharmacotherapeutics in the upcoming future perspectives by enhancing the half-life of the drug employing the floating extended-release attributes.