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Facial skin treatments with laser resurfacing, dermabrasion, and chemical peels were responsible for a significant portion of the 2.7 million cosmetic procedures performed in 1998. Perioral wrinkles are a common problem for which plastic surgical consultation is obtained. The aim of this study was to compare and quantify the advantages and disadvantages of laser resurfacing versus dermabrasion in the treatment of perioral wrinkles. Twenty female patients provided informed consent and participated in the study. Half of the perioral area was treated with dermabrasion and half was treated with the UltraPulse CO2 laser. The two procedures were compared using high-quality photographs; a biophysical evaluation of skin color, hydration, and mechanical properties; and patient evaluation of outcomes. Photographs were evaluated by 10 board-certified plastic surgeons who were blinded to the treatment methods. The laser treatment had a significantly higher erythema score at 1 month and a small but significantly greater improvement in perioral wrinkles at 6 months. Thirteen subjects selected the laser treatment as producing the best result, despite the greater intraoperative pain for this procedure. Biomechanical measurements suggest that the laser treatment produced a skin state more similar to skin in younger patients, presumably with higher levels and/or greater organization of the collagen and elastin. Patient preference was inferred from the resurfacing method that they would recommend to a friend. Although the laser was selected as the best result in a majority of cases, patient preference was equally distributed between the two treatments. The authors think that by studying and quantifying the biophysical changes that occur as a result of CO2 laser resurfacing, greater improvements in restoring actinic damage (e.g., wrinkles) can be achieved. Patients consider more than the objective skin changes from a resurfacing technique when making a recommendation to a friend.