The revolution in nanotechnology has lead to the development of various dosage forms such as vesicular drug delivery and in particular liposomes, niosomes, proniosomes, aquasomes, bilosomes etc. The disad-vantages exhibited by the liposomes, niosomes can be overcome through introduction of proniosomes which are compact liquid crystalline structures and convert to niosomes upon hydration. The investigation is focused on development and optimization of Betaxolol proniosomes using three square factorial design technique with the aid of design expert 11.0 ® trial version. The optimization technique prefers choles-terol and span 60 as independent variables and drug content, vesicular size, and entrapment efficacy as dependent variables. The design generated total 13 formulations among which F10 exhibited 98.1% drug content and 97.3% of entrapment efficacy. In view of other parameters, F10 exhibits 6.5 pH, 3.8 ve-sicular size and follows diffusion mechanism with anomalous drug transport. Hence, the obtained results specify that F10 is optimized and can be opted for commercialization.