Introduction: Cefadroxil is a first-generation cephalosporin and is very effective against Gram positive and Gram negative infections. Cefadroxil is an antibiotic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional Cefadroxil tablets produce rapid and relatively high peak blood level and require frequent administration to keep the plasma drug level at an effective range. The present study was carried out with an objective of preparation and in vivo evaluation of floating tablets of using Cefadroxil as a model drug using Eudragit polymers to improve oral bioavailability of Cefadroxil floating tablets by increasing gastric residence time. Methodology: Floating controlled-release cefadroxil tablets were prepared by direct compression method. Tablets were formulated using Eudragit polymers (Eudragit-RLPO & Eudragit-RSPO), with Sodium alginate (SA) and Carbomer (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content etc. Consequently, 6 months of physical stability studies and in vitro-in vivo gastro-retentive studies were conducted. Results and Discussion: The result of in vitro dissolution study showed that the drug release profile could be controlled by increasing the concentration of Eudragit-RLPO. The optimized formulation (F20) containing Eudragit-RLPO showed 99.17% drug release at the end of 24h. Changing the viscosity grade of Eudragit-RLPO had no significant effect on drug release profile. The optimized formulations (F20) containing sodium bicarbonate 40mg per tablet showed desired buoyancy (floating lag time of about 20 min and total floating time of >24h). Optimized formulation (F20) followed diffusion controlled zero order kinetics and fickian transport of the drug. FTIR and DSC studies revealed the absence of any chemical interaction between drug and polymers used. The best formulation (F20) was selected based on in vitro characteristics and was used in vivo radiographic studies by incorporating BaSO4. These studies revealed that the tablets remained in the stomach for 24h in fasting human volunteers and indicated that gastric retention time was increased by the floating principle, which was considered desirable for the absorption window drugs. Studies to evaluate the pharmacokinetics in vivo showed better bioavailability, area under the concentration time curve, elimination rate constant and half-life than marketed product. Conclusion: In conclusion, in order to suggest a better drug delivery system with constant favorable release, resulting in optimized absorption and less side effects, formulated Eudragit based cefadroxil floating controlled-release tablets can be a promising improves candidate therapy. Keywords: Cefadroxil, Eudragit RLPO, Eudragit RSPO, sodium alginate, PVP K30, magnesium stearate and micro crystalline cellulose, Radiographic studies.