The eastern oyster (Crassostrea virginica) is a reef-forming organism commonly found in estuaries throughout the Atlantic and Gulf coasts of North America. Eastern oyster reefs provide several ecosystem services, including water filtration, habitat diversity, and storm surge protection, among others. Oyster abundance has declined precipitously during the past century along the Atlantic and Gulf coasts as a result of overfishing, disease and predation, and large-scale human-mediated events. Given the importance of oysters, both ecologically and economically, there have been significant efforts during the past 20 y to reestablish and/or restore oysters to historical levels. Successful reef restoration depends on choosing sites that optimize survival, which requires an understanding of the environmental factors that influence the life stage of an oyster. For most restoration projects, time and budget constraints prevent long-term field studies; therefore, modeling is often used to determine the best locations for restoration. In this study, we developed a spatially explicit, flexible, 4-parameter habitat suitability index model that can be used to determine locations suitable for restoration of eastern oyster reefs throughout the western Atlantic and Gulf coasts. The model captures the minimum environmental parameters required for successful restoration suitability and was applied in 2 studies: (1) Chesapeake Bay, a data rich environment, and (2) northern Gulf of Mexico (western Mississippi Sound), a data poor environment. It illustrates the implications of using data of varying quality when applying the model for identifying restoration potential. In both locations, the model was most sensitive to the presence of appropriate substrate, but not as sensitive to salinity values. This model provides a scientifically based support tool for natural resource managers and project planners, and local conditions may require further consideration.