Objectives: The purpose of the work was to develop gastro retentive floating tablets of Dicloxacillin sodium using different ratios of HPMC K 100M, Xanthan gum, Guar gum. Sodium bicarbonate is used as a gas generating agent. Dicloxacillin sodium is used to treat a wide variety of bacterial infections and has a half-life of about 2 hr. Methods: Gastro retentive floating tablets containing 270 mg of dicloxacillin sodium were prepared by wet granulation method employing different ratios of polymers. Results: The formulated tablets were evaluated for precompression parameters and were in the acceptable limits. Post-compression parameters such as weight variation, hardness, friability, swelling index, floating lag time and total floating time were also evaluated. The formulation F3 with HPMC K 100M showed 98.87% of drug release at the end of 12 hr, maintained integrity of tablets and have an optimum floating lag time of 90±0.14 sec and total floating time of 12 hr. The optimized formulation F3 was fitted to various kinetic models and the results showed that F3 formulation followed Zero order kinetics with an R 2 value of 0.993. The mechanism of drug release from F3 formulation was non-fickian diffusion. Conclusion: The study concluded that, among all the developed formulations, F3 formulation floated up to 12 hr with maximum drug release and can be considered as promising formulation.