The aim of this study was to explore the risk factors of schistosomiasis japonica in China, using a hierarchical multi-level model with individuals nested within villages. Methods: A cross-sectional survey of schistosomiasis japonica was conducted in 16 villages in the Chinese province of Hunan. A multi-level modeling technique (HLM version 6.04) was used to assess risk factors of schistosomiasis. The results from this multi-level model were compared with those from a conventional single-level logistic regression model. Results: A total of 10 245 individuals were enrolled in this study, of whom about 4.1% were infected with Schistosoma japonicum. In the multi-level model analysis, individual level variables such as gender, age, and occupation, and village level variables such as type of S. japonicum endemic area, drinking water source, sewage treatment, June temperature, and April rainfall were associated with schistosomiasis japonica infection. Conventional single-level logistic regression analysis selected more independent variables, and had narrower confidence intervals around the corresponding regression coefficients. In particular, per capita income, precipitation in October, and density of infected snails were statistically significant in the conventional singlelevel logistic regression analysis but not in the multi-level model.