Ionotropic gelation method was used to entrap Ketoprofen (KP) into calcium alginate beads. KP is one of the non steroidal anti-inflammatory drugs (NSAIDs); it has a short half life (1.5-2 h) and deleterious side effects on GIT such as irritation and ulceration. Beads were investigated in-vitro for possible sustained drug release and in-vivo as a gastro-protective system for KP. The curing time of beads in CaCl2 solution was determined and process variables, such as polymer concentration, polymer/drug ratio and co-entrapped polymers (Gelatin (G), Hydroxy propyl methyl cellulose acetate succinate (HPMCAS) and ethyl cellulose (EC)) were analyzed for their influence on bead properties. On the basis of differential scanning colorimetry (DSC) and IR- spectroscopy, alginate was found to be compatible with KP. Scanning electron microscopy (SEM) photographs showed that the prepared beads were spherical and small (about 1 mm diameter) with small cracks and fissures on the surface. KP encapsulation efficiencies were high (>90%), also results showed that, release profile in 0.1M HCl (pH 1) was slow. while in phosphate buffer (pH 7.4), complete drug release was exhibited for all formulations within 2 h. There was no improvement concerning the retarding of drug release with co-entrapped polymers. The mechanism of release was depending on swelling and erosion of beads. The swelling behavior was strongly dependent on pH of the medium; such a pH sensitive swelling could be advantageous for orally administered drug vehicles especially for acid sensitive drugs or drugs that have adverse effects on GIT. The Ulcerogenic effect of the free drug on the stomach was compared to that of drug encapsulated in alginate beads using rats. Results showed a significant mucoprotective effect of alginate beads compared to the free drug. In conclusion, alginate beads can be used as enteric coated formulations rather than ideal sustained release formulations.