We studied the effect of the carbonic anhydrase inhibitor methazolamide in 25 patients with essential tremor (ET) in a double-blind, placebo-controlled trial. Tremor assessment included patient self-reporting of functional disability, clinical rating of motor tasks and tremor severity, and accelerometric measurements. There was no significant difference between methazolamide and placebo in any of the assessments. Side effects, paresthesias, sedation, headaches, and gastrointestinal symptoms were common. Only two patients elected to remain on the drug after the study. Methazolamide has only limited efficacy in the treatment of essential tremor.