Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disease of the central nervous system. The experience in children is limited. We retrospectively reviewed our experience with 20 ADEM patients (10 females, 10 males) with age of onset before 18 years old in Taiwan to clarify the clinical manifestations, neuroimaging findings, and the relationship between ADEM and multiple sclerosis (MS). The age at onset ranged from 4 months to 15 years. Seventeen (85%) children had a recent infectious prodrome. Children presented most often with acute consciousness disturbance (70%) and motor deficits (55%). Seizures occurred in 10 (50%), but only one child developed epilepsy in follow-up. Brain magnetic resonance imaging (MRI) evaluations done in all patients revealed multifocal lesions, mainly in subcortical white matter (80%), brainstem (65%), basal ganglia (55%), cerebellum (45%), thalamus (40%), and periventricular white matter (35%). Spinal cord MRI was performed in 9 patients and all of them showed abnormal lesions. Eleven patients were treated with high-dose intravenous methylprednisolone pulse therapy, and only one had mild long-term neurological sequelae. Among the 20 patients, five had long-term neurological sequelae and one died. Three patients fit the criteria of multiphasic disseminated encephalomyelitis, in which two developed MS in follow-up. Another patient with ADEM turned out to be MS two years later. We concluded that seizures are not uncommon in ADEM, but the subsequent development of epilepsy is rare. Long-term prognosis of ADEM is generally good. Because recurrence of ADEM is not uncommon, long-term follow-up of those children with ADEM is needed to distinguish between ADEM and MS.