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The aim of the study was to assess the safety and efficacy of a novel fractional CO2 laser for the treatment of genitourinary syndrome of menopause (GSM).Women presenting with GSM and meeting study criteria were enrolled. Examinations at baseline and follow-up (3 mo after final treatment) evaluated dilator tolerance and vaginal pH. Visual analog scales were used to assess pain, vaginal burning, vaginal itching, vaginal dryness, dyspareunia, and dysuria; Vaginal Health Index scores were completed before each treatment and at follow-up; Female Sexual Function Index and Short Form 12 questionnaires were also completed. Participant satisfaction was measured on a 5-point Likert scale (1 = very dissatisfied, 5 = very satisfied). Women received three laser treatments, 6 weeks apart.Thirty women participated (mean age 58.6 ± 8.8 y). None withdrew or were discontinued due to an adverse event; three were lost to follow-up. Average improvement in visual analog scale scoring was 1.7 ± 3.2 for pain, 1.4 ± 2.9 for burning, 1.4 ± 1.9 for itching, 6.1 ± 2.7 for dryness, 5.1 ± 3.0 for dyspareunia, and 1.0 ± 2.4 for dysuria; improvement in average Vaginal Health Index and Female Sexual Function Index scores were statistically significant (P < 0.001). Twenty-five of 30 participants (83%) showed increase in comfortable dilator size at 3-month follow up. Before the second and third treatments, 86.6% (26 of 30) of women reported they were better or much better than at the previous treatment; 26 of 27 women (96%) were reportedly satisfied or extremely satisfied at follow-up.In this sample, the data suggest that the fractional CO2 laser is effective and safe for treatment of the symptoms associated with GSM.