Objective: Enterovirus 71(EV71) and Coxsackievirus A16(Cox A16) are the main pathogens of the Hand,foot,and mouth disease(HFMD). In this study,we compared clinical manifestation and outcome of HFMD induced by EV71 and Cox A16. Methods: A total of 570 HFMD patients treated in Nanjing Children’s Hospital Affiliated with NJMU were enrolled in this study from January to June in 2011. Throat swabs were collected from these patients for detecting virus by real time PCR. Manifestations,outcomes for these patients were analyzed. Results: The average age of 350 patients with EV71 infection was (2.5 ± 1.7) years. The average age of 220 patients with CoxA16 infection was (2.3 ± 1.3) years. Patients with EV71 infection had a significantly longer hospitalization period(P < 0.001). The main manifestations were fever with a temperature above 39℃ and lasted longer (P < 0.01). EV71-induced myoclonic jerk,oral ulcer were significantly higher (P < 0.05). EV71-induced cough,febrile seizure were significantly lower (P < 0.05). However,central nervous system complications were significantly higher (P < 0.05). About 3.7% of EV71-infected children had neurologic sequela,and five patients with EV71 infection died of encephalitis and cardiopulmonary failure. All the patients with CoxA16 infection showed total recover. Conclusion: The main pathogen of HFMD was EV 71 in Nanjing region from January to June in 2011. Compared with those patients infected by Cox A16,the children with EV71 infection had serious clinical manifestations and worse outcomes.