Abstract Objective: Alternating hemiplegia of childhood (AHC) is a rare and intractable disorder. The etiology and standard therapy of alternating hemiplegia of childhood remain unknown. The long-term effects of flunarizine or topiramate on patients with alternating hemiplegia of childhood are still not clear. Methods: Fifteen patients were investigated in this study. Their neurological disturbance and mental retardation after drug therapy were evaluated. Results: Nine patients treated with flunarizine therapy and three children with topimarate treatment presented with shorter duration or less frequency of the hemiplegic attacks. These drug responsive patients also showed improvements on neurological disturbance including eye movement disorder, choreo-athetotic movements, dystonia and ataxia. However seizure episodes and cognitive impairments were not alleviated in AHC with long-term drug therapy. Conclusions: The findings from the present study support flunarizine or topitamate as the rational treatment for alternating hemiplegia of childhood.