Severe hyperhidrosis affects 2.8% of the population and can be emotionally devastating. First-line therapy employs topical agents such as aluminum chloride (AC), but efficacy and tolerability vary widely. Botulinum toxin type A (BTX-A) is FDA-approved for the treatment of primary focal axillary hyperhidrosis unresponsive to topical therapy. A single-center, randomized, parallel, open-label, 12-week study was performed to compare the efficacy and safety of BTX-A with 20% AC for the treatment of primary focal axillary hyperhidrosis. Twenty-five subjects were randomized to either BTX-A or AC treatment, and were evaluated for treatment response by an improvement of > or =2 grades on the Hyperhidrosis Disease Severity Scale (HDSS). At week 4, 92% of the subjects in the BTX-A group achieved treatment response compared with 33% of the subjects in the AC group. Overall, treatment with BTX-A was more effective and provided greater patient satisfaction than with AC. Treatment with AC was effective and tolerated in 29% of the subjects.