Background and Objective: To evaluate histologically the characteristics of repetitive Er:YAG laser exposure of skin in combination with cryogen spray cooling (CSC), and its potential as a method of laser skin resurfacing. Study Design/Materials and Methods: Rat skin was irradiated in vivo with sequences of 10 Er:YAG laser pulses (repetition rate 20 Hz, pulse duration 150 or 550 ms, single-pulse¯uence 1.3±5.2 J/cm 2 ). In some examples, CSC was applied to reduce epidermal injury. Histologic evaluation was performed 1 hour, 1 day, 5 days, and 4 weeks post-irradiation. Results: A sequence of ten 550-ms pulses with¯uences around 2 J/cm 2 resulted in acute dermal collagen coagulation to a depth of approximately 250 mm, without complete epidermal ablation. CSC improved epidermal preservation, but also diminished the coagulation depth. Four weeks after irradiation, neo-collagen formation was observed to depths in excess of 100 mm. Conclusion: Dermal collagen coagulation and neo-collagen formation to depths similar to those observed after CO 2 laser resurfacing can be achieved without complete ablation of the epidermis by rapidly stacking long Er:YAG laser pulses. Application of CSC does not offer signi®cant epidermal protection for a given dermal coagulation depth.