Abstract\nBackground-This study was designed for evaluation of the clinical variables of severe cases with Hand, Foot and Mouth Disease (HFMD). It would help to improve the diagnosis and treatment of severe HFMD.\nMethods-475 severe HFMD patients during an outbreak in 2009 were divided into two groups: one group, 140 cases, is treated with mechanical ventilation as extremely severe cases and another is 335 cases treated without mechanical ventilation to analyze the clinical features and management outcomes, retrospectively. \nResults-The results show that there is no distinctive difference of sex, age and maximum body temperature between these two groups. Compared to non-mechanical ventilation group, the blood lactic acid，white blood cell, and plasma glucose of patients in the mechanical ventilation group were both significantly elevated compared to those found in the group of non-mechanical ventilation; And the clinical manifestation such as poor spirit, convulsion, myoclonus, skin rash, duration of fever, and breathing rate were more serious than those of the non-mechanical ventilation group.\nConclusion-Our study showed that the elevated lactic acid with leukocyte and glucose levels in patients, treated with mechanical ventilation as extremely severe cases with HFMD are related to disease activation, and disease course is more severe in patients. Therefore, we suggest that evaluating the elevated lactic acid with leukocyte and glucose levels in severe cases of HFMD patients will help clinicians to predict for indication of tracheal intubation and mechanical ventilation during disease course and improve outcomes.