The present study was aimed at developing and evaluating polymeric beads with sustained drug release and prolonged gastric residence. The polymeric beads were prepared by solvent evaporation technique using Cellulose acetate (CA) as matrix former for model drug Ibuprofen (IBF) in 1% aqueous polyvinyl alcohol (PVA) solution as external phase. Effects of various formulation variables like drug-polymer ratio, external phase viscosity, external phase volume, solvent ratio and processing variables like stirring speed, temperature of external phase, stirring time, and drying temperature on properties of beads were accessed. Drug polymer ratio was optimized to maximize the percent yield and drug content. Beads were characterized for shape, size, percent buoyancy, entrapment efficiency, floating time and in-vitro drug release. The scanning electron micrographs show a porous nature of beads thereby enabling them to float. When used alone, CA though formed good beads, drug entrapment efficiency was very low. To increase the drug entrapment, CA was partially substituted with Ethyl cellulose EC (up to 20%) to modulate drug entrapment efficiency and optimize the bead properties including drug release. Beads formed with higher viscous solution either formed agglomerates or dumbbell shaped structures. The optimized batches have uniform size distribution, remained buoyant for more than 18 hours and sustained the drug release up to 10 hours with diffusion through matrix being the main drug releasing mechanism.