BACKGROUND: Shanxi Province has historically reported a high prevalence of NTDs. In order to establish baseline rates for NTDs and discuss the risk factors associated with sociodemographic, maternal characteristics, and geographic factors, we performed the present study using an approach combining population and hospital-based methodologies. METHODS: We used χ2 and Fisher's exact tests to evaluate variation in the prevalence by selected covariates and computed crude ORs and 95% CIs. Adjusted odds ratios (AORs) were performed using logistic regression with all the covariates included in the model. RESULTS: The overall NTD prevalence during the 3 year study period was 199.38 per 10,000 births, with a higher NTD prevalence clustered in 46 villages within this geographic area. However, no statistical significance was found between NTD prevalence and the elevation of the villages or their distance from coal plants. AORs revealed women aged 20 and above had a lower risk of NTDs compared to those younger than 20 (AOR range 0.4–0.5). A higher risk of NTDs was observed among female infants (AOR 1.50; 95% CI: 1.04–2.17), women with four or more previous births (AOR 2.80; 95% CI: 1.20–6.52), and a previous history of birth defects (AOR 3.23; 95% CI: 1.46–7.12). CONCLUSIONS: This study has documented a high prevalence of NTDs in Shanxi. Similar variations to other reports were found in the risk of NTDs by maternal demographic characteristics and a clustering of NTDs in certain villages that require further exploration. Birth Defects Research (Part A), 2007. © 2007 Wiley-Liss, Inc.