We examined the relationship between meteorological parameters and hand, foot and mouth disease (HFMD) activity. Meteorological data collected from 2000 to 2004 were tested for correlation with HFMD consultation rates calculated through the sentinel surveillance system in Hong Kong. The regression model constructed was used to predict HFMD consultation rates for 2005–2009. After adjusting for the effect of collinearity, mean temperature, diurnal difference in temperature, relative humidity, and wind speed were positively associated with HFMD consultation rates, and explained HFMD consultation rates well with 2 weeks' lag time (R2=0·119, P=0·010). The predicted HFMD consultation rates were also also well matched with the observed rates (Spearman's correlation coefficient=0·276, P=0·000) in 2005–2009. Sensitivity analysis showed that HFMD consultation rates were mostly affected by relative humidity and least affected by wind speed. Our model demonstrated that climate parameters help in predicting HFMD activity, which could assist in explaining the winter peak detected in recent years and in issuing early warning.