Abstract : Purpose: The objective of the research work was to design novel proniosomes containing highly potent drug tretinoin (TRT). Methods: In present work, proniosomes were prepared by three known methods viz; coacervation phase separation, slurry and slow spray coating method and characterized for Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), zeta potential, pH, viscosity, drug content, % entrapment efficiency (%EE), spreadability, in vitro drug release and stability studies. Results: Formulation F7 prepared by coacervation phase separation showed highest in vitro drug release. Small multilamellar vesicles, with size ranging from 100 to 200 nm were successfully obtained in SEM. In the second method proniosomes were prepared by rotary flash evaporator and in vitro release of P7 formulation was found to be best and in controlled pattern. The size of vesicles came to be in range 10 -300 nm in SEM while the shape of vesicles was spherical, no drug crystal was found. Then proniosomes were prepared by slow spray coating method, in which A8 formulation showed best and controlled release pattern. SEM OF formulations by third method showed spherical vesicles and in size range 50 -100 nm. Zeta potential, %EE, pH, viscosity, conductivity and spreadability were found within acceptable limit. The best formulation (F7) amongst all twenty seven formulations was applied to TEM which showed satisfactory result. Conclusion: Thus, proniosomes proved to have better potential for transdermal delivery of TRT over conventional gel formulations.