Aim: This study aimed to formulate and evaluate grainsetron HCl transdermal patches to reduce the problems associated with oral delivery of the drug and enhancement of drug permeation through the skin. Methods: Grainsetron HCl loaded transdermal patch were prepared by solvent evaporation method. Six formulations were prepared based on the two independent variables, type of surfactant and Phospholipid: Edge activator ratio and were evaluated for their vesicle size, PDI, and entrapment efficiency. The optimized formulations were incorporated into transdermal patches, which were evaluated for physicochemical properties ex-vivo permeation, skin irritancy, and stability studies. Result: Ex-vivo skin permeation study of optimized formulation NEB3 plot of cumulative amount of drug release versus time generate for Permeation studies. From this plot, permeation kinetic parameters such as permeation flux, permeability coefficient and enhancement ratio were calculated. The results showed that NEB3 with 30% w/w had a flux of 174.25±1.04 and released 65.21% in 720 minutes. The results of the in-vivo skin irritation study indicate that the optimized batch NEB3 did not cause significant irritation on rat skin for up to 14 days and was safely used for up to 24 hours. The stability of the optimized formulation (NEB3) was assessed at various temperatures over a period of 30 days. The optimized formulation was assessed for various parameters such as appearance, weight variation, folding endurance, tensile strength, and drug content. The evaluation showed no significant changes in the formulation under room, oven, and cold temperatures. Conclusion: The study concluded that transdermal patches of Grainsetron HCl could be used as a potential approach with effective transdermal delivery for the management of chemotherapy induced vomiting.