The US Environmental Protection Agency's (EPA's) Total Maximum Daily Loads (TMDL) program promotes nationally consistent approaches for documenting the progress in restoring impaired waters. EPA's TMDL program provides tracking systems comprising both database and geographic information systems (GIS) mapping components. The GIS mapping is implemented using the National Hydrography Dataset (NHD). The EPA and the US Geological Survey have developed an enhanced NHD product (NHDPlus) that is applied in this study to define an interstate waters framework for the conterminous United States. This NHDPlus-based framework provides an efficient watershed-oriented approach for selecting interstate waters. Greater consistency in approaches for interstate waters is essential for providing improved techniques for integrated assessment and management programs. Improved analysis tools for interstate waters are clearly important from a federal perspective. Insights based on tools for federal interstate waters are also of interest for state water quality agencies when they deal with complicated interjurisdictional challenges that can require leveraging support from a wide range of stakeholders. Summaries are provided on the degree of consistency documented for inland waters where states have provided TMDL listing GIS information for shared interstate NHD reaches, and summaries are provided on the patterns for interstate assessments organized according to the ecoregions developed for EPA's Wadeable Streams Assessment. The relevance of this interstate waters framework in leveraging the TMDL program to provide enhanced support for watershed oriented management approaches is also explored.