Neuromyelitis optica (NMO) is a relapsing inflammatory condition characterized by selective involvement of the optic nerves and spinal cord. Humoral immune mechanisms play a role in the pathogenesis of NMO. The therapeutic efficacy of plasmapheresis (PP) has been reported in the cases that were poorly controlled with other treatments. Herein, we report four patients with NMO who underwent PP following intensive intravenous corticosteroid therapy. All patients showed definite functional improvement following one to five plasma exchanges. To prevent relapse, these patients were treated with oral prednisolone in combination with azathioprine or cyclophosphamide. Two of the four patients also underwent intermittent PP because treatment with oral agents was unsuccessful. In conclusion, when treatment with oral immunosuppressants is ineffective in reducing recurrences of NMO, an additional PP session should be attempted.