BACKGROUND Although enterovirus 71 has caused epidemics associated with significant morbidity and mortality, its transmission has not been thoroughly investigated. OBJECTIVE To investigate enterovirus 71 transmission and determine clinical outcomes within households. METHODS Prospective family cohort study to investigate patients at a children's hospital in Taiwan and family members of these patients who had signs and symptoms suggestive of enterovirus 71 between February 2001 and August 2002. Patients and household members underwent clinical evaluations, virological studies, questionnaire-based interviews, and were followed up for 6 months. METHODS Enterovirus 71 infection, defined as a positive viral culture from a throat or rectal swab, or the presence of IgM or a 4-fold increase in neutralizing antibody in serum; and clinical syndromes, defined as asymptomatic; uncomplicated symptomatic; and complicated; with unfavorable outcomes of sequelae or death. RESULTS Ninety-four families (433 family members) had at least 1 family member with evidence of enterovirus 71 infection. The overall enterovirus 71 transmission rate to household contacts was 52% (176/339 household contacts). Transmission rates were 84% for siblings (70/83); 83%, cousins (19/23); 41%, parents (72/175); 28%, grandparents (10/36); and 26%, uncles and aunts (5/19). Of 183 infected children, 11 (6%) were asymptomatic and 133 (73%) had uncomplicated illnesses (hand, foot, and mouth disease, herpangina, nonspecific febrile illness, upper respiratory tract infection, enteritis, or viral exanthema). Twenty-one percent (39/183) experienced complicated syndromes including the central nervous system or cardiopulmonary failure. During the 6-month follow-up, 10 died and 13 had long-term sequelae consisting of dysfunction in swallowing, cranial nerve palsies, central hypoventilation, or limb weakness and atrophy. Age younger than 3 years was the most significant factor associated with an unfavorable outcome in children (P =.004). Among 87 infected adults, 46 (53%) were asymptomatic, 34 (39%) had nonspecific illnesses of fever, sore throat, or gastrointestinal discomfort, and 7 (8%) had hand, foot, and mouth disease. There were no complicated cases in adults. CONCLUSIONS Enterovirus 71 household transmission rates were high for children in Taiwan and severe disease with serious complications, sequelae, and death occurred frequently. In contrast, adults had a much lower rate of acquisition of the infection and much less adverse sequelae.