OBJECTIVE To evaluate the effectiveness of tizanidine in treating intention myoclonus. DESIGN Case series. SETTING Inpatient rehabilitation center. PARTICIPANTS Three subjects whose activities of daily living were impaired due to intention myoclonus related to mitochondrial encephalomyopathy, stroke, and multiple sclerosis (MS). INTERVENTION Tizanidine. MAIN OUTCOME MEASURES Reduction in intention myoclonus and change in score on the FIM instrument. RESULTS The patient with mitochondrial encephalomyopathy had left upper- and lower-extremity intention myoclonus; the patient with stroke had left upper intention myoclonus; and the patient with MS had right upper- and left lower-intention myoclonus. In the patient with mitochondrial encephalomyopathy, the FIM score increased from 90 to 103 points over 2 days of tizanidine. The stroke patient's FIM score improved only from 74 to 79 after 4 weeks of tizanidine. The patient with MS improved from 83 to 101 after 6 days of tizanidine. All 3 patients had almost full resolution of the intention myoclonus. All continued on tizanidine except the patient with stroke, who had minimal gains and a low systolic blood pressure. None of the patients experienced significant sedation or hypotension. CONCLUSIONS Tizanidine may be a safe and effective option for treating intention myoclonus that occurs in a variety of neurologic conditions.