Neuroleptic-induced akathisia (NIA) is a common, sometimes incapacitating adverse effect of anti-psychotic medication. Zolmitriptan is a selective 5-HT(1D) agonist. We aimed to determine its anti-NIA efficacy in comparison to propranolol. Thirty-three neuroleptic-treated patients were randomly allocated in a double-blind design to receive either 7.5 mg/d of zolmitriptan or 120 mg/d of propranolol for 3 consecutive days, followed by 3 days without any anti-NIA treatment. Patients were assessed at baseline and on days 3 and 7 by the Barnes Akathisia Rating Scale (BARS), PANSS, HAMD, HAMA, Pulse, and Blood Pressure. Both groups showed improvement of akathisia (BARS) along the treatment period, with significant effect for time but not for group. No significant differences were found between the groups in all other measurements. Taken together, zolmitriptan was found to be as effective as propranolol for the treatment of NIA. Further placebo-controlled studies are warranted.