Frequently occurring skin irritancy and flare-up reactions impede the use of topical tretinoin for acne vulgaris due to poor patient compliance. Liposome encapsulation improves penetration into the skin and local tolerability in animals. We investigated efficacy and local tolerability of liposomal tretinoin in man. In a double-blind study 20 patients with uncomplicated acne vulgaris received liposomal tretinoin (0.01 %) on one side of the body and a commercial gel preparation with either 0.025% or 0.05% on the other once daily for 10 weeks. Comedones and papules/pustules were counted every 2 (–4) weeks. Then also redness, scaling, and burning were rated according to a four-point scale. Moreover, the patients noted skin irritancy in a diary on a daily base. With conventional tretinoin the gels were equally efficacious and equally well tolerated. Liposomal tretinoin also appeared equipotent to the reference gels. There may even have been a slightly more rapid clearing of comedones following the liposome preparation. With respect to skin irritancy, however, liposomal tretinoin was superior. As rated by the patients, liposome encapsulated tretinoin induced less burning (mean cumulative score 2.7 ± 1.2) than the 0.025% gel (16.1 ± 7.1) and the 0.05% gel (9.7±4.1) gel and less erythema (1.8±0.7) than the 0.025% gel (11.4 ± 3.8; (P < 0.05).="" liposomal="" tretinoin="" was="" also="" better="" tolerated="" according="" to="" the="" rating="" by="" the="" investigator.="" liposomal="" encapsulation="" of="" tretinoin="" allows="" reduction="" of="" the="" concentration="" of="" the="" active="" agent="" without="" a="" decline="" in="" efficacy="" for="" acne="" vulgaris.="" since="" local="" tolerability="" is="" thus="" increased,="" liposomal="" tretinoin="" should="" favor="" the="" acceptance="" of="" this="" treatment="" by="" the="">