The aim of the present study was to prepare sustained-release tablet of diltiazem hydrochloride, a soluble drug, in which the drug release complied with the specification of USP XXX Methods: Direct compress process was used to formulate to develop the sustained-release tablet formulations with Kollidon SR, HPMC, Eudragit RS PO 100, Precirol ATO 5. Drug release was tested according to USP XXX Results: Drug released from the formulation using the mixture of HPMC and X (a cellulose derivative which is capable fast swelling) was best fitted to zero-order kinetic and complied with the specification of USP XXX Conclusions: The present results provided evidence that diltiazem hydrochloride sustained-release tablet can be prepared and be used for effective treatment of hypertension and angina pectoris.