Context: Niosomes are the non-ionic surfactant vesicles obtained on hydration of synthetic non-ionic surfactants. These are the promising vehicles for effective transdermal drug delivery. Objective: The present research work was aimed to develop niosomal-based transdermal buflomedil hydrochloride patch containing a stable formulation with improved drug permeation. Materials and methods: Niosomes were prepared by solvent evaporation method using 3 factorial design. All the formulations were evaluated for vesicle size, zeta potential and percent entrapment efficiency. Optimized niosomal and liposomal formulation were loaded into a patch system. All the patches were then characterized for drug-excipient interaction study, scanning electron microscopy, pharmacotechnical properties and in vitro permeation studies. Result: F9 formulation having optimum vesicle size (10.09 ± 1.2 µm), highest zeta potential (-85.4 ± 0.56 mV) and maximum percent entrapment efficiency (97.09 ± 0.11%) was selected as optimized formulation. In case of liposomes, formulation F12 was selected. Patches loaded with niosomes showed 95.12 ± 1.19% cumulative amount of drug permeated as compared to liposomal vesicle-loaded patches which showed 82.21 ± 1.24% and control patches 70.10 ± 1.33%. Discussion: Flux, permeation rate and permeability coefficient were found to be higher in case of niosomal patches as compared to liposomal patches and control patches. Surfactant present in niosomes act as a penetration enhancer which contribute in the permeation enhancement of buflomedil hydrochloride from niosomes. Conclusion: Thus, it was concluded that niosomal vesicles represented to be an efficient and stable vesicular carrier for transdermal delivery of buflomedil hydrochloride.