Wetlands deliver a suite of ecosystem services to society. Anthropogenic activities, such as wetland drainage, have resulted in considerable wetland loss and degradation, diminishing the intrinsic value of wetland ecosystems worldwide. Protecting remaining wetlands and restoring degraded wetlands are common management practices to preserve and reclaim wetland benefits to society. Accordingly, methods for monitoring and assessing wetlands are required to evaluate their ecologic condition and outcomes of restoration activities. We used an established methodology for conducting vegetation-based assessments and describe a case study consisting of a wetland condition assessment in the Prairie Pothole Region of the North American Great Plains. We provide an overview of an existing method for selecting wetlands to sample across broad geographic distributions using a spatially balanced statistical design. We also describe site assessment protocols, including vegetation survey methods, and how field data were applied to a vegetation index that categorized wetlands according to ecologic condition. Results of the case study indicated that vegetation communities in nearly 50% of the surveyed wetlands were in very poor or poor condition, while only about 25% were considered good or very good. Approximately 70% of wetlands in native grasslands were categorized as good or very good compared to only 12% of those in reseeded grasslands (formerly cropland). In terms of informing restoration and management activities, results indicated that improved restoration practices could include a greater focus on establishing natural vegetation communities, and both restored and native prairie wetlands would benefit from enhanced management of invasive species.