Famotidine, a histamine H2 receptor antagonist is absorbed only in the initial part of gastro intestinal (GI) tract and has less bioavailability. Hence the drug was formulated as gastro-retentive drug delivery systems in the form of mucoadhesive microspheres to prolong its residence time in the stomach and improve its absorption. The microspheres of famotidine were prepared by emulsification-ionic gelation technique using mucoadhesive polymers such as Sodium Alginate, Carbopol 934P and HPMC in different ratios. All the formulations were subjected to particle size and shape analysis, drug content, in vitro mucoadhesion evaluation and in vitro drug release studies. Encapsulation efficiency was found to be in the range of 75.95 – 86.76 %. Formulations containing Carbopol 934P showed mucoadhesion for a period of more than 8h. Drug release decreased with increase in mucoadhesive polymer content in the microspheres. Among the formulations, for two different polymer combinations, F2 and F4 showed maximum drug release in a sustained fashion at the end of 7 h and 8h respectively with superior mucoadhesion. The rate of drug release follows zero order kinetics. Stability studies for a period of 8 weeks did not show appreciable changes with respect to particle size and drug content.