Lafutidine (LAF) a newly developed histamine H2-receptor antagonist with absorption window makes it a good candidate to be prepared as floating drug delivery system. The current study involves formulation and in- Vitro evaluation of lafutidine as floating microspheres. Different formulation variables that affect the physicochemical properties of the prepared microspheres besides to the drug release behavior were investigated. Fourteen formulas were prepared by emulsion (o/w) solvent evaporation method using Ethyl cellulose (EC) as the polymeric matrix and tween 80 (TW80) as an emulsifying agent. The prepared formulas were evaluated for their percentage buoyancy (%), Percentage yield (%) and Entrapment efficiency (EE %). The results obtained by formulations were in the range of 64.5±1.885% to 96.8±1.22%, 70.4% to 86, 8% and 27±1.39% to 91.2±1.21% respectively. Formulas (FLF10 and FLF10A ) which prepared using 3:1 of EC : lafutidine ratio but with different stirring speed show desirable physicochemical properties and optimum, prolonged in vitro drug release profile and about 92.62% and 95.31% of drug dose release within 14 hrs respectively. It can be concluded that the floating microspheres of lafutidine can be made by emulsion solvent evaporation technique with good gastro retention ability and with expected better drug bioavailability