Objective To investigate the epidemic characteristics of etiological agents and analyze the clinic differences in children with hand,foot and mouth diseases in Shanghai.Methods Collection 551 specimens including vesicle fluid,stool and throat swabs to detect the pathogens.The positive rates were tested by RT-PCR assay with Entcrovirus conscnsus primer and specific primer for Enterovirus 71 (EV71)and Coxsackie A16(CoxA16),respectively.Results Out of 357 patients,the overall positive rate was 79.7％.CoxA16 infection was mainly popular in 2009,EV71 was mainly popular in 2011.The epidemic characteristics of enterovirus infection within 2009-2011 had significant differences (P =0.005).The positive rate of vesicle fluid was highest.The concurrent rate of fever and tendency to be frightened had significant differences in three patients' groups.The count of the peripheral white blood cells and the ratio of the neutrophil in the patients with EV71 infection was higher than that in the patients with CoxA16 or PE infection.Conclusion HFMD showed alternant epidemic characteristics at different times of enterovirus infection in Shanghai.Analyzing the differences of clinic characteristic of EV71 and CoxA16 infection is helpful to prevent and control EV71 infection.