Isoxsuprine hydrochloride is a peripheral vasodilator. It is advisable to prepare the drug in sustained release dosage forms to improve patient compliance and to achieve a steady state blood level with minimum side effects. Different hydrophilic and hydrophobic polymers in addition to their combinations were used in different ratios to select the best level of the matrix forming material that provides the most sustaining effect. The effect of different types and concentrations of polymers on the release rate of the drug was investigated. The drug release decreased by increasing the concentration of the polymer in all the studied formulations. Tablet formula containing either 30% (w/w) HPMC 15000 or 30% (w/w) Eudragit RSPM gave the most sustaining effect among the single polymers. The drug release rate from tablets prepared using polymer blends is slower compared to that from those containing single polymers. The slowest drug release was obtained from tablet formulae containing: drug, 10% (w/w) HPMC 15000 and 40% (w/w) Eudragit RSPM and drug, 10% (w/w) Eudragit RSPM and 40% (w/w) Eudragit RLPO. The release of isoxsuprine HCl from matrices prepared using single polymer followed Higuchi's diffusion model. However, zero-order release kinetics was elucidated for the release of isoxsuprine HCl from the investigated polymer blends in phosphate buffer (pH 6.8).