Background and objective: Enterovirus 71 (EV 71) infections may result in the rapid progression of cardiopulmonary failure. Early endotracheal intubation is considered to be of primary importance. However, the appropriate timing for this is still not known. The aim of this study is to investigate the timing of intubation of children with fulminant EV71 infection. Material and Methods: From March 1998 to May 2012, patients with severe EV71 infection who were admitted to the pediatric intensive care unit of the National Cheng Kung University Hospital were enrolled in this study. Medical records were retrospectively reviewed. The patients were classified into three groups in accordance with the outcome of intubation. We used rhombencephalitis grading to describe the neurological presentation of these patients. The study was approved by the institutional review board. Results: There were a total of 105 patients enrolled. Of these, 77 patients were in Grade I, and only three of them needed intubation, who were, however, soon extubated within 24 h. There were 10 patients in Grade II; nine of them needed intubation. In total, 18 patients belonged to Grade III, and all of them need to be intubated. We then compared the outcome of intubation of grades II and III. There was only one patient out of the nine patients in grade II who experienced failed extubation due to the progression of the disease. Among grade III patients, only four patients were successfully extubated. We also listed clinical parameters to determine which one could be a sign that indicated intubation. Comparing the favorable outcomes, cranial nerve involvement was a good indicator for the timing of intubation. Conclusions: This study showed that early intubation in Grade II provides favorable outcomes and improves morbidity and mortality. We also found that if cranial nerve involvement was present, then early intubation is indicated.