The purpose of the research was to prepare and evaluate Roxatidine acetate HCl floating microspheres by ionotropic gelation method. Fourteen formulations were prepared, among all the formulations F13 was selected as optimized formulation based on the micromeretic and evaluation parameters including drug release studies. In the in vitro release study of formulation, F13 showed 95.65% drug release after 12 h in a controlled manner, which is desired for disease like peptic ulcer. In vitro release profiles from optimized formulation F13 were applied on various kinetic models. The best fit with the highest correlation coefficient was observed in zero order and Higuchi model, indicating diffusion controlled principle. The innovator Rotane 150 mg conventional tablet showed the drug release of 96.45% within 1 h. FT-IR and DSC analyses confirmed the absence of drug-polymer interaction. The results obtained from evaluation and performance study of different types of Roxatidine microspheres showed that system may be useful to achieve a controlled drug release profile, reduce the dose of drug, dosing frequency and improve patient compliance when compared with marketed product. Key words: Roxatidine, buoyancy, HPMC, gum olibanum, microspheres.