Acne vulgaris is the most prevalent disorder in the period before puberty when increased adrenal androgen level causes enlargement of the sebaceous glands and it increased the production of sebum on the face, chest, and back. This disease is caused due to interaction between many causative agents or pathogenic components which lead to formation of the acne and those are seborrhea, follicular hyper keratinization, microbial formation of pilosebaceous unit by Propionibacterium acne and arrival of inflammatory mediators. Tazarotene is a well-known retinoid related to vitamin A that belongs to an acetylenic class of retinoid, used in the management of acne. Oral administration of Tazarotene causes changes in bone morphology after prolonged exposure to high doses, which also exhibit teratogenicity but this does not occur with topical delivery. Ethosomes are non-invasive delivery carriers enabling drugs to reach to the bottom of the skin layers and/or the system and transfersomes are the self-adaptable ultra-deformable flexible elastic bilayer vesicles composed of phospholipids able to penetrate through the pores of skin even smaller than its size. Present research aims the comparative evaluation of ethosomal and transfersomal gels loaded with Tazarotene in the treatment of acne. In the present study, ethosomes and transfersomes were formulated by the cold method and hand-shaking method, respectively, followed by loading of Tazarotene and development into gel formulation. The formulated gel samples were evaluated for in vitro release study, in vitro permeation study, in vitro anti-acne study, in vivo percutaneous permeation study by CLSM, and in vivo anti-acne study. The results proved that both the formulated ethosomal and transfersomal gels have better permeation through the skin but ethosomal gel showed better release in comparison to transfersomal gel, also final gels exhibited the anti-acne potentiality.