Background: Axillary hyperhidrosis is a common condition that can be personally distressing and can interfere with professional and social life. Intracutaneous injections of botulinum toxin type A (BTXA) have recently been shown to induce an effective but temporary anhidrosis, usually for 4 to 6 months. High-dose BTXA was shown to have a lower relapse rate, but it remained unclear whether it could induce a prolongation of the antihidrotic effect. Objective: Our aim was to evaluate the long-term effectiveness of “high-dose” botulinum toxin therapy in axillary hyperhidrosis, the response to repeated treatment, and the possible side effects. Methods: In an open study in a university medical center, 47 patients with axillary hyperhidrosis unresponsive to previous therapies were treated with intracutaneous injections of botulinum A toxin. A total dose of 200 U of BTXA was used per axilla. Patients were followed up for periods up to 29 months. The main outcome measures were patients' satisfaction with the antihidrotic effect, response to repeated treatment, and safety of treatment. Results: Within 6 days of the injection of BTXA, all patients reported cessation of excessive sweating. The follow-up was 17.0 ± 8.3 months (range, 3-29 months). The relapse rate within 12 months of treatment was 4 of 34 patients (11.8%). The longest relapse-free interval observed was 29 months. Twenty-two patients showed a relapse-free interval of 19 months or more. The number of patients with at least 12 months of remission was significantly higher with 200 U of botulinum toxin than with lower doses reported in current literature (P < .05). Relapsed patients (a total of 6/47) showed an unchanged excellent response to a second or third treatment. The only side effect was temporary pain and burning during the injections. No muscular weakness, insensitivity, or systemic reactions were observed. Conclusion: High-dose BTXA treatment is capable of prolonging the antihidrotic effect of intracutaneous BTXA in most patients for more than 19 months. It reduces the percentage of relapses after 12 months of follow-up to less than 12%. So far, there is no clinical evidence of the induction of neutralizing antibodies. High-dose treatment seems to be as safe as low-dose treatment. (J Am Acad Dermatol 2002;46:536-40.)