Clopidogrel Bisulphate is an Antiplatelet (Inhibitor of P2Y12 ADP platelet receptors) used in the treatment of Heart Attack, Ischemic Stroke, Acute Coronary Syndrome and Platelet Aggregation Inhibition. It is incompletely absorbed from the gastrointestinal tract and has an oral bioavailability of only 50%, while remaining drug is excreted unchanged in faeces. This is because of poor absorption in lower gastrointestinal tract. It undergoes little or no hepatic first pass metabolism and its elimination half-life is 6 to 7 hours. Therefore, it is selected as a suitable drug for the design of a gastro-retentive floating drug delivery system (GFDDS) with a view to improve its oral bioavailability. In the present study, an attempt was made to design and optimize GFDDS of Clopidogrel Bisulphate using hydroxyl propyl methyl cellulose of different viscosity grades (K100LV and K4M) as the polymers and sodium bicarbonate as a gas generating agent, to reduce floating lag time. The tablets were prepared by direct compression method. Six batches of preliminary trial formulations were designed and the designed batches of formulations were evaluated for hardness, friability, weight variation, swelling index, in vitro drug release pattern, stability and drug-excipient interaction. Estimation of Clopidogrel Bisulphate in the prepared GFDDS was carried out by extracting drug with methanol and measuring the absorbance at 220 nm. In vitro drug release studies were performed in USP tablet dissolution test apparatus employing paddle stirrer at 50 rpm using 900 ml of 0.1N HCl maintained at 370.5C as the dissolution medium. Majority of the designed GFDDS of Clopidogrel Bisulphate indicated that the optimized formulation F6 followed the korsmeyer - peppas model with n value of 0.499 i.e. Drug release was observed by Non-Fickian diffusion. The optimized formulation (F6) thus possibly enhanced the oral bioavailability of the drug.