The objective of the present study was to develop once-daily sustained-release matrix tablets of propranolol used in the treatment of hypertension, angina pectoris, and many other cardiovascular disorders. The constrained mixture experimental design was used to prepare systematic model formulations, which were composed of Eudragit RSPO and different viscosity grades of HPMC (Methocel E50 and Methocel K15M CR). The matrix tablets were prepared by direct compression process. The prepared tablets were evaluated for various physico-chemical parameters. In vitro release profile was check for 24 hrs to evaluate the SR matrix tablet of propranolol. Increase in Eudragit RSPO and HPMC concentrations or increase in viscosity grades of HPMC polymers (Methocel E50 and Methocel K15M CR) resulted in a significant decrease in propranolol release. Administration of propranolol in a sustained release dosage would be more desirable for antihypertensive effects by maintaining the plasma concentrations of the drug well above the therapeutic concentration. From in vitro dissolution profile, Batch F4 was prepared with blend of Eudragit RSPO (80 mg), Methocel E50 (60 mg) and Methocel K15M CR (80 mg) where drug release was about 98.11%.