Transdermal patches of Papaverine hydrochloride were prepared by solvent casting method using ethyl cellulose: PVP, PVA: PVP and eudragit RL-100: eudragit RS-100 in different ratios. The physicochemical parameters like flexibility, thickness, smoothness, weight variation, moisture content, hardness and tensile strength were evaluated and found to be flexible, uniform thickness and weight, smooth, good drug content (92 to 96%) and little moisture absorption. The in-vitro diffusion studies were carried out using modified Keshery-Chein cell with cellophane as diffusion membrane and the formulation followed Higuchi diffusion mechanism. The formulation containing PVA: PVP as polymers showed faster release rate (hydrophilic polymers) compared to eudragit RL-100: eudragit RS-100 (hydrophobic polymers) or combination of hydrophilic and hydrophobic polymers (Ethyl cellulose and PVP). The stability studies indicated that all the patches maintained good physicochemical properties and drug content after storing the patches in different storage conditions. Compatibility studies indicated that there was no interaction between the drug and polymers. In vivo studies showed that papaverine hydrochloride helps in decreasing the effect of isoproterenol induced myocardial necrosis.