OBJECTIVES. Several large outbreaks of enterovirus 71 infections have occurred in Taiwan during the past decade. Brainstem encephalitis was the most common neurologic complication. This study was designed to determine the long-term cognitive and motor outcomes of children with enterovirus 71 brainstem encephalitis. METHODS. We conducted a prospective follow-up study of children who met the case definition for enterovirus 71 brainstem encephalitis. Subjects were stratified into isolated brainstem encephalitis (stage II), autonomic nervous system dysregulation (stage IIIa), and pulmonary edema (stage IIIb). The subjects and their parents or guardians were interviewed using structured questionnaires and received comprehensive cognitive and neurologic examinations. Motor coordination, visual-motor skill, and intellectual ability were evaluated. RESULTS. Follow-up studies were conducted in 63 previously healthy children with enterovirus 71 brainstem encephalitis (49 stage II, 7 stage IIIa, and 7 stage IIIb). The mean time to follow-up was 2.8 ± 1.0 years (range: 1.4–4.9 years). Boys outnumbered girls by 3 to 2. The mean age at diagnosis was 2.4 ± 1.4 years (range: 0.3–7.1 years). The most common abnormal neurologic findings on admission were altered consciousness (47.6%), followed by abnormal activities of daily living (52.4%), cerebellar dysfunction (17.5%), and cranial nerve palsy (15.9%). At follow-up, 51 of 63 children had no detectable deficits. Among the remaining 12 children, 3 died during the follow-up. The remaining 9 children (14.3%) had residual deficits. Two of these with stage IIIb disease continued to have severe motor and respiratory failure. CONCLUSIONS. Residual defects were still present in a significant proportion of children with enterovirus 71 brainstem encephalitis at >2 years after their hospitalization. Children with stage II disease were most likely to have residual cerebellar defects. Those with stage IIIb disease continued to have severe respiratory and motor impairment. Long-term follow-up of this cohort is needed to determine the ultimate prognosis.