BACKGROUND: As the demand for minimally invasive rejuvenation is increasing, micropeel resurfacing using Erbium:Yttrium Aluminum Garnet (Er:YAG) laser 2940 nm has been reported for the treatment of photoaged skin without ablation of the epidermis. However, little is known about the efficacy and underlying histologic changes associated with this type of treatment. AIMS: The aims of this study are to evaluate the clinical effect and objectively quantify the histological changes in response to multiple sessions of Er:YAG laser 2940 nm mini-peels. PATIENTS AND METHODS: Six female volunteers of Fitzpatrick skin type III-IV and Glogau's class I-III wrinkles were subjected to six microresurfacing peels at 2-week intervals using Er:YAG 2940 nm laser at subablative fluences of 2-3 J/cm(2) to treat periorbital rhytides. Quantitative evaluation of collagen types I, III, and VII, newly synthesized collagen, total elastin, and tropoelastin was performed by histochemistry and immunohistochemistry coupled with computerized morphometric analysis at base line, end of treatment, and 3 months post-treatment. RESULTS: Compared to the base line, evaluation of volunteers revealed obvious clinical improvement in response to Er:YAG mini-peels. Collagen types I, III, and VII, as well as newly synthesized collagen, together with tropoelastin showed a statistically significant increase in response to treatment, while the mean level of total elastin was significantly decreased in response to treatment. However, this was followed by regression of improvement at 3 months post-treatment but was still better than baseline. CONCLUSIONS: This study revealed that multiple Er:YAG mini-peels is a promising treatment option for photoaging as it reverses the signs of photoaged skin with little downtime and side effects. However, to maintain the short-term improvement achieved after treatment, continued Er:YAG 2940 nm laser mini-peels is required.