This study involved developing a matrix-type transdermal therapeutic system comprising of ondansetron hydrochloride with 7:3 ratio of hydrophilic and hydrophobic polymeric combinations using solvent evaporation technique. The effects of permeation enhancers were studied at the concentrations of 2.5% and 5% using essential oils such as menthol oil, eucalyptus oil, clove oil, lemon grass oil and the blend of best volatile oil with Tween 20 dibutyl phthalate and glycerin were used as plasticizers. Formulated patches were evaluated for thickness, folding endurance, drug content, percent moisture absorption, percent moisture loss, tensile strength and water vapour transmission rate. There was no physicalchemical incompatibility between the drug and the polymers. The results of in vitro drug release studies showed that the blend of menthol oil and Tween 20 exhibited maximum release. The optimized formulation was found to be stable during the stability studies. The developed transdermal patches increase the efficacy and improve the bioavailability.