Objective: To assess the incidence, severity, and spectrum of neurologic toxic effects associated with administration of amiodarone hydrochloride. Design: Retrospective medical record analysis of cardiac patients treated with amiodarone between January 1, 1996, and July 31, 2008. Setting: Residents of Olmsted County, Minnesota, treated at the Mayo Clinic. Patients: The Mayo Clinic medical records of all adult Olmsted County residents prescribed amiodarone between January 1, 1996, and July 31, 2008, were reviewed and all possible neurologic adverse effects that might be attributable to amiodarone were tabulated. Main Outcome Measures: Risk factors and clinical characteristics of patients developing neurologic problems were compared with those who did not. Results: Over the 151 months of analysis, 707 patients were treated with amiodarone. Among these patients, the cumulative incidence of likely amiodarone neurotoxic effects was 2.8%; 1.6% of all amiodarone-treated patients were referred to Neurology for a neurotoxic reaction. Neurologic problems included tremor, gait ataxia, peripheral neuropathy, and cognitive impairment. The primary risk factor for amiodarone neurotoxic effects was duration of treatment, not age, drug dose, sex, or indication for therapy. Where this could be assessed, the adverse effects were usually but not always reversible. Conclusions: Amiodarone infrequently causes clinically significant neurologic toxic effects. Substantially higher estimates of neurotoxic effects in the early amiodarone era may be related to a much higher daily dose.