Hand, foot and mouth disease (HFMD) is an important public health issue in mainland China, including Jiangsu Province. The main purpose of this study was to depict the epidemiological characteristics of HFMD and evaluate the effects of meteorological variables on its dynamics via spatiotemporal analytic methods, which is essential for formulating scientific and effective prevention and control strategies and measures. In total, 497,910 cases of HFMD occurred in the 2009-2013 period, with an average annual incidence of 126.3 per 100,000 in Jiangsu. Out of these, 87.7% were under 5 years old with a male-to-female incidence ratio of 1.4. The dominant pathogens of the laboratory-confirmed cases were EV71 and CoxA16, accounting for 44.8% and 30.6% of all cases, respectively. Two incidence peaks were observed in each year, the higher occurring between April and June, the lower between November and December. The incidence ranged between 16.8 and 233.5 per 100,000 at the county level. The incidence in the South of the province was generally higher than that in the northern regions. The most likely spatiotemporal cluster detected by space–time scan analysis occurred in May-June of 2012 in the southern region. Average temperature and rainfall were positively correlated with HFMD incidence, while the number of days with rainfall ≥ 0.1mm, low temperature, high temperature and hours of sunshine were negatively related. Particularly, relative humidity had no relationship. In conclusion, the prevalence of HFMD in Jiangsu Province has an obvious feature of seasonality. The etiological composition changed dynamically and might be a latent driving force for the temporal variation of the incidence of HFMD. A moderately warm environment promotes the transmission of the HFMD viruses, while particularly cold and hot climate conditions restrain their transmission.