OBJECTIVE： To optimize the formulation of Roxatidine acetate hydrochloride （ROX） sustained-release tablets. METHODS： ROX sustained-release tablets were prepared by direct powder compression method. Central composite design-response surface methodology was used to optimize the formulation with composite index of 1， 4， 8 h in vitro accumulative release rate as index， using mass ratio of lactose/microcrystalline cellulose （MCC） （m/m）， ethyl cellulose （EC） amount and HPMC amount as factors. Validation test was also conducted. RESULTS： The optimal formulation was as follows as ROX 75 mg， lactose 45 mg， MCC 91 mg， EC 65 mg， HPMC 124 mg， micropowder silica gel 2 mg. 1， 4， 8 h in vitro accumulative release rates of prepared sustained-release tablets were （30.7±0.5）％， （65.8±0.7）％， （89.4±0.6）％， respectively. Related errors of them to predicted value were 0.6％， 0.8％， 1.2％， respectively. CONCLUSIONS： ROX sustained-release tablets are prepared successfully， and sustained-release effect is consisted with the expected effect.