Background Duration of effect and effectiveness limit current options for treating axillary hyperhidrosis. A new microwave procedure for treatment of axillary hyperhidrosis has been tested. Study Design/Materials and Methods Adults with primary axillary hyperhidrosis were enrolled in a randomized, sham-controlled, blinded study. Subjects were required to have a Hyperhidrosis Disease Severity Scale (HDSS) score of 3 or 4 and baseline sweat production greater than 50 mg/5 min. Procedures were administered using a proprietary microwave energy device that isolates and heats target tissue. Responders were defined as subjects reporting a HDSS score of 1 or 2. Subjects were followed for 6 months (sham group) or 12 months (active group). Results Thirty days after treatment, the active group had a responder rate of 89% (72/81), and the sham group had a responder rate of 54% (21/39) (P <.001). Treatment efficacy was stable from 3 months (74%) to 12 months (69%), when follow-up ended. Adverse events were generally mild, and all but one resolved over time. Conclusions The procedure demonstrated statistically significant, long-term efficacy in sweat reduction. As with any new procedure, findings from this first investigational device study identified optimization strategies for the future.