The erbium:yttrium-aluminium-garnet (Er:YAG) laser has recently been used in the fractional resurfacing of photo-aged skin. Our study evaluated the results after one single session of fractional resurfacing with Er:YAG. Thirty women participated in the study, with an average age of 46 years, skin types from II to IV, and wrinkle grades I to III. The 2,940 nm Er:YAG system used (Pixel, Alma Laser, Israel) had variable pulse durations (1 ms to 2 ms) and energy densities (800 mJ/cm(2) to 1,400 mJ/cm(2)) which, together with the number of passes (four to eight), were selected as a function of wrinkle severity. All patients received only one treatment. Postoperative side effects were evaluated. The number of wrinkles was documented with clinical photography and was scored. Histological assessment was carried out on two patients before and 2 months after treatment. All patients completed the study. Of the patients, 93% reported good or very good improvement of the degree of their wrinkles, with a satisfaction index of 83%. Pain was not a problem during treatment, and there were no side effects except for in one phototype IV patient, who had hyperpigmentation. Histology 2 months after the single treatment demonstrated younger morphology of both the epidermis and dermis, with improvement of the pretreatment typical elastotic appearance. At the parameters used in our study, only one treatment session of Er:YAG laser could achieve effective skin rejuvenation, with effects recognized in both the dermis and, more importantly, the epidermis. This regimen offers an interesting alternative to the conventional approach of multi-session fractional resurfacing.