Objective: The main aim of this study was to design and characterise betamethasone di-propionate loaded transfersomes (BD-T); as a topical formulation for the treatment of localized plaque psoriasis. 3 ) was applied to study the effects of three independent variables: drug content, type of surfactants and surfactant contents on particle size (PS), entrapment efficiency (EE %), zeta potential (ZP), polydispersity index (PI) and drug release profiles. The optimized BD-T was formulated as a hydrogel using 5% sodium carboxymethyl cellulose. The gel was characterized for viscosity, drug content, in vitro drug release and stability. A comparative clinical study was performed on 20 patients with psoriasis to investigate the effect of BD-T gel and the marketed betamethasone dipropionate (BD) cream. Methods Results:The optimized BD-T formulation containing 50 mg betamethasone dipropionate (BD) and 5 mg tween 80 showed spherical unilamellar vesicles with an average particle size of 242.80, % EE of 90.19%, ZP of-15.00 mV, PI of 0.407 and K0 Keywords: Transfersomes, Betamethasone dipropionate (BD), Localized psoriasis of 4.290 mg/hr. The formulation showed good stability at 4 °C and 25 °C for 6 mo. The results revealed significant clinical improvement and a significant increase in safety and tolerability with BD-T gel compared with BD cream. Conclusion:As a conclusion, BD-T was found to be more effective, safe and tolerable for the treatment of psoriasis compared with the marketed product.