An oral dosage form containing gastro-retentive floating tablets forms a stomach-specific drug delivery system for the treatment of hypertension. Valsartan belongs to the BCS class II (poo Classification System). It is desirable to improve the extent of bioavailability (23%).  The objective of the present study was to apply design of experiment to optimize floating drug delivery of valsartan by employing 22 factorial design.  Improvement of the aqueous solubility of valsartan was done by solid dispersions using hot melt extrusion technique.  Plasdone S630 copovidone is a variable carrier and drug to carrier ratio of 1:2 was optimized.  Valsartan floating tablets were prepared by employing factorial design (22), where HPMC K15M (X1) and pregelatinized starch (X2) were independent variables and drug dissolution was the dependent parameter (Y1) to prepare matrix tablets.  The factorial analysis, steepest ascent method was utilized for obtaining optimized formulation. In vitro evaluation, In vivo radiographic study and biopharmaceutical analysis in rabbits for valsartan optimized formulation (FT-5). Floating lag time (FLT) for valsartan optimized formulation (FT-5) was 15 s and total floating time (TFT) of the tablets was about 33 h, which was satisfactory.  A four-point (1 h, 4 h, 8 h and 16 h) dissolution analysis gave satisfactory dissolution profile up to 24 h.  The release kinetics of valsartan optimized formulation (FT-5) followed zero order and the release mechanism was found to be Korsemeyer Peppas model, i.e. swelling type.  The dissolution efficiency for valsartan floating tablets was 1190.89% against the marketed formulation of 39.77%. The accelerated stability profile of valsartan optimized formulation (FT-5) was evaluated in terms of drug content and percent cumulative dissolution of valsartan in 24 h, in a 6 months study.  In vivo X-ray image study for valsartan optimized formulation (FT-5) indicated the presence of intact tablet up to 12 h in gastric region of rabbit.  The biopharmaceutical analysis in rabbits was conducted for valsartan optimized formulation (FT-5). The HPLC method was established and validated for the in vivo analysis.  The Cmax was 453.2 ng/mL compared to that of the marketed tablets (522.4 ng/mL).  The mean residence time (MRT) for the valsartan optimized formulation (FT-5) was 14.82 h as against 4 h for marketed tablet.  The relative bioavailability of valsartan optimized formulation (FT-5) was 650% higher than the marketed tablet.  To overcome the poor bioavailability of valsartan, it was suitably modified using hot-melt extrusion for improving therapeutic outcome. In conclusion, gastro-retentive drug delivery system is an excellent approach for improving the bioavailability of valsartan.