OBJECTIVE: To prepare Diphenidol hydrochloride double-layer osmotic pump tablets, and study its in vitro release characteristics. METHODS: Double-layer compressing technique and film coating technology were conducted to prepare Diphenidol hydrochloride double-layer osmotic pump tablets. The in vitro releases of it, Difenidol hydrochloride tablets in market, self-made Difenidol hydrochloride single-layer osmotic pump tablets were compared. RESULTS: The formulation was as follow as diphenidol hydrochloride 75 mg, sodium chloride 10 mg, low-molecular-weight polyoxyethylene 15 mg and right amounts of 5% PVP K30 ethanol solution. Booster layer was high-molecular-weight polyoxyethylene 60 mg, sodium chloride 20 mg, PVP K30 6 mg, right amounts of magnesium stearate. 12 h cumulative release (Q) of prepared double-layer osmotic pump tablets reached 80%, and the release was in line with zero-order kinetic equation. Q15 min of Difenidol hydrochloride tablets had reached 90%; Q12 h of Difenidol hydrochloride single-layer osmotic pump tablets was only 51.14%. CONCLUSIONS: The prepared Difenidol hydrochloride double-layer osmotic pump tablets have sustained release effect, with more complete drug release within 12 h than single-layer one.