OBJECTIVE: To study the epidemiologic characteristics of hand-foot-mouth disease (HFMD) in Guiyang between 2008 and 2010. METHODS: The epidemiologic characteristics of HFMD were analyzed by descriptive statistical methods based on the data from the China Information System for Disease Control and Prevention. RESULTS: A total of 27383 cases of HFMD were recorded in Guiyang between 2008 and 2010. The incidence of HFMD increased from 66.4439/100000 in 2008 to 163.9276/100000 in 2009 and 471.5515/100000 in 2010 (P<0.01). The mortality rate was 0.1026/100000 in 2010, which was significantly lower than in 2009 (0.2821/100000) (P<0.05). HFMD occurrence showed seasonality and reached a peak between April and June. HFMD cases were commonly noted in children under 5 years old, and especially in children under 3 years old. The main detected pathogen was human enterovirus 71 (EV17) in 2009. Whereas in 2010 the disease was mainly caused by CoxA16 and other intestinal viruses. CONCLUSIONS: The incidence of HFMD in Guiyang increased year by year from 2008 to 2010, but the mortality rate decreased year by year. HFMD occurrence showed an obvious seasonality. HFMD was common in children under the age of five. The main pathogens of this disease included EV17, CoxA16 and other intestinal viruses.