In 1998, an epidemic of enterovirus 71 (EV 71) infection occurred in Taiwan. The purpose of this study was to assess the epidemiology of EV 71 infection in Taiwan. Between March 1998 and December 2005, a total of 1,548 severe cases of hand-foot-mouth disease and herpangina (HFMD/HA) was reported to the Center for Disease Control in Taiwan. A seasonal variation in number of severe cases was observed, with the annual peak in second quarter. Deaths from severe HFMD/HA varied from year to year (chi(2) for trend = 6.781, P = 0.009). Most (92%) cases occurred in children </= 4 years of age. Children infected with EV 71 had higher risk of pulmonary edema/hemorrhage and encephalitis than those not infected. Infection with EV 71 has emerged as an important infectious disease causing serious clinical illness and deaths of young children. Vaccine development is recommended to prevent future EV 71 infections.