Conservation is costly, and choices must be made about where to best allocate limited resources. I propose a regional evolutionary diversity and endangerment (RED-E) approach to prioritization of endangered species. It builds off of the evolutionary diversity and global endangerment (EDGE) approach, but will allow conservation agencies to focus their efforts on species in specific regions. I used the RED-E approach to prioritize mammal and bird species listed under the U.S. Endangered Species Act (ESA), as well as to make a ranking of species without ESA critical habitat (CH), as a practical application. Regional conservation approaches differ significantly from global approaches. The RED-E approach places a high significance on the level of endangerment of a species, but also allows for very distinct species to have increased prioritization on the RED-E list. Using the CH RED-E list, the U.S. government could begin focusing resources toward endangered and genetically diverse species.