Ecological risk assessment (ERA) is a new field of study for evaluating the risks associated with a possible eco-environmental hazard under uncertainty. Regional ERA is more complex than general ERA, as it requires that risk receptors, risk sources, risk exposure, uncertainty and especially spatial heterogeneity all be taken into account. In this paper, a five-step process of regional ERA is developed and tested through a wetland case study in the Yellow River Delta in China. First, indices and formulas are established for measuring degrees of ecological risk and damage to ecosystems. Using a combination of remote sensing data, historical records and survey data, and with the assistance of GIS techniques, the indices and formulas are then applied to the wetland in the study area. On the basis of the assessment results, we propose a number of countermeasures for the various risk zones in the Yellow River Delta.