The aim of the present study was to assess the effect of floods on the transmission of schistosomiasis in the Yangtze River valley, People's Republic of China. Retrospective analyses of malacologic, clinical and epidemiologic data, covering a 22-year period, were carried out to elucidate the dispersal patterns of intermediate host snails (Oncomelania hupensis), and acute and chronic infections with Schistosoma japonicum in humans in relation to floods. Potential O. hupensis habitats in years with floods were 2.6-2.7 times larger than in years when water levels were normal. Both the density and infection rate of O. hupensis dropped in the first two years after a flood, but significantly increased in the third year. The number of acute cases with schistosomiasis japonica was markedly higher in years characterized by floods; on average, 2.8 times more cases were observed when compared to years that the Yangtze River had normal water levels. In view of our findings, emergency responses are warranted as soon as possible after the occurrence of a flood in order to avoid or mitigate the reemergence and spread of human schistosomiasis in the People's Republic of China.