The aim of the study was formulation and evaluation of a proniosomal transdermal gel as vesicular drug delivery system for improving stability of formulation and sustaining drug release of Ritonavir, an HIV antiviral drug. Initial studies focussed on the formulation parameters that influence the manufacturing process by using non ionic surfactant and then evaluation parameters for optimization of formulation. The drug excipients compatibility studies were carried out by DSC studies and FTIR spectra revealed that the drug and excipients used were compatible with each other. The evaluation of proniosomes shows an entrapment efficiency range of 61.60±2.05 to 91.74±0.54%. The optimized batch shows the encapsulation efficiency 91.74±0.54%, vesicle size 246.48±3nm and drug content 96.41±0.74%. The drug release studies of proniosomal gel was carried out by diffusion through cellophane membrane % drug release was found to be 89.09±1.5%, Rate of spontaneity 14.54±0.95 mm3x1000, pH 7.2±1.45, viscosity 4298±2.05 cp, spreadability 48±0.23 mm. The optimized formulation was evaluated for morphology and structure of proniosomes (SEM) shows spherical in shape, Zeta Potential was found to be -56.21. This study provided the evidence that the proniosomal vesicles are valuable as the transdermal drug delivery for ritonavir to sustaining the drug release and enhance the stability of formulation.