The upper Mississippi River (UMR) contains diverse, dense, and reproducing assemblages of native freshwater mussels. In the case of an injury to mussels and their habitats, such as a hazardous material spill, train derailment, or barge grounding, resource managers have few restoration strategies. Resource managers need a means to document, quantify, and mitigate adverse effects on mussels resulting from injury. Habitat equivalency analysis (HEA), developed for use with a wide variety of habitat types, is a restoration scaling technique that compares ecological services lost from injury to ecological services gained through restoration actions. The U.S. Fish and Wildlife Service and Iowa Department of Natural Resources modified the HEA for use with native mussels. The mussel HEA has been applied within the UMR to estimate the quantity of restoration needed to compensate the public for injuries to mussels due to contaminant spills and construction projects. Our objective was to describe the UMR HEA for a general audience and assess if the four biological input variables used in the mussel HEA were reasonable based on literature values. We also evaluated the performance of HEA under a range of input scenarios. Although the input estimates used in HEA were within ranges reported in the peer-reviewed literature or were supported by professional judgment in the absence of peer-reviewed literature, outcomes of the mussel HEA were highly variable and would benefit from additional research to reduce uncertainty in the biological inputs. The application of HEA to mussels provides resource managers with a tool to quantify mussel-related ecological services lost from injury and to guide restoration efforts in the UMR.