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Background and Objective: Hyperhidrosis (HH) is associated with impairments in quality of life (QOL) and elevated anxiety. Microwave thermolysis is a newer treatment that reduces sweating, yet effects on QOL and emotional symptoms have not been examined. Two treatment sessions are recommended to achieve 80% amelioration of clinical HH. We hypothesized that microwave thermolysis would reduce sweat severity, improve QOL, and reduce anxiety in young adults suffering from axillary HH in a prospective clinical trial., Study Design/materials and Methods: We enrolled 24 young adults (mean age = 23.57 years, 54% female) with elevated scores on the Hyperhidrosis Disease Severity Scale. All participants received one session of microwave thermolysis, and 83% received two sessions. Participants completed measures of sweat severity, QOL, generalized anxiety, social anxiety, social avoidance, and anxious/depressive mood symptoms at baseline; post-first treatment; and following second treatment., Results: At baseline, all participants had severe sweating; 87.5% had impaired QOL, 75% had elevated social anxiety, 50% with generalized anxiety, 48% with social avoidance, and 38% with anxious/depressed mood. Paired samples t tests indicated significant improvements from baseline to first procedure, including decreased sweating (t(21) = 5.68, P < 0.001), improved QOL (t(23) = 4.97, P < 0.001), and decreased generalized anxiety (t(23) = 8.11, P < 0.001), social anxiety (t(22) = 4.55, P < 0.001), mood symptoms (t(21) = 3.81, P = 0.001), and social avoidance (t(22) = 3.12, P = 0.005). After second treatment, further improvements were noted in sweating (t(18) = 3.28, P = 0.004) and QOL (t(18) = 3.83, P = 0.003), and a marginal trend for generalized anxiety (t(19) = 1.96, P = 0.064)., Conclusion: There were significant improvements in sweat severity, skin-specific QOL, generalized anxiety, social anxiety, anxious/depressive symptoms, and social avoidance. The majority of the psychosocial benefit appears to emerge after one treatment of microwave thermolysis, whereas the level of sweat severity and QOL continued to show further improvements after a second treatment. Results would suggest that although two microwave thermolysis sessions are needed for maximal treatment optimization of axillary HH, patients may experience significant benefits in improving psychosocial functioning after just one session. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc., (© 2020 Wiley Periodicals, Inc.)