Abstract: Objective To understand the risk factors of hand foot and mouth disease with different clinical features, and provide scientific evidence for the disease control. Methods The epidemic data of HFMD, the data of mild, severe and death cases of HFMD in Zhejiang from March, 2009 to April, 2010 were collected to conduct analysis by using SPSS 13.0 software. Results The risk factors of severe cases of HFMD included children being outside child care settings, being floating population, living in rural area or outskirt, going to vaccination clinic 7 days prior to the onset and family with multichildren aged 14 years. The risk factors of death cases included the first medical care seeking in low grade hospital, high misdiagnosis rate and children being reared by grandparents. Most severe and death cases were detected to be EV71 positive. Conclusion Severe cases mainly occurred among children outside child care settings, in floating population and living in rural area or outskirt with the risk factors of going to vaccination clinic before the onset and family with multichildren. Most deaths were due to the misdiagnosis at low grade hospitals, and many of these children were reared by their grandparent. EV71 was the major pathogen to cause severe and death cases of HFMD.