Objective: This study was designed to describe the clinical features and management outcomes of severe hand, foot and mouth disease (HFMD). Subjects and Methods: Data on 147 severe HFMD patients during an outbreak in 2009 were analyzed. Results: Most patients were under 3 years of age; 102 (69.4%) were boys. All had skin rashes and fever of '38Â°C. All (n = 147, 100%) showed signs of central nervous system involvement, such as lethargy (n = 124, 84.4%), myoclonic jerks (n = 76, 51.7%), or drowsiness (n = 34, 23.1%). Respiratory symptoms were mainly tachypnea (n = 112, 76.2%) or bradypnea (n = 21, 14.3%). Common cardiovascular symptoms included tachycardia (n = 134, 91.2%) and hypertension (n = 23, 15.5%). Chest X-ray showed increased markings in 76 (51.7%) or consolidation in 44 (29.9%). Hyperglycemia and elevated blood lactic acid levels were found in 127 (86.4%) and 130 (88.4%), respectively. Positive enterovirus EV71-PCR was found in 113 (76.9%). All patients were treated with mechanical ventilation for 61.2 ± 12.8 h (range, 40'96 h), as well as mannitol, dexamethasone, gamma globulin and ribavirin. Dopamine, dobutamine or amrinone was administered in 58.5, 51.0 and 21.8%, respectively. Three patients (2%) died during hospitalization. All others had a full recovery and were discharged after 14.2 ± 1.6 days (range, 12'17 days). Conclusion: Central nervous and cardiorespiratory systems were involved in the patients with severe HFMD. Fasting blood glucose and lactic acid levels increased in the majority of patients. Mechanical ventilation and supportive pharmacotherapy were associated with a good clinical outcome in these patients.