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The tallgrass prairie is one of the most severely affected ecosystems in North America. As a result of extensive conversion to agriculture during the last century, as little as 1% of the original tallgrass prairie remains. The remaining fragments of tallgrass prairie communities have conservation significance, but questions remain about their viability and importance to conservation. We investigated the effects of fragment size, native plant species diversity, and location on invasion by exotic plant species at 25 tallgrass prairie sites in central North America at various geographic scales. We used exotic species richness and relative cover as measures of invasion. Exotic species richness and cover were not related to area for all sites considered together. There were no significant relationships between native species richness and exotic species richness at the cluster and regional scale or for all sites considered together. At the local scale, exotic species richness was positively related to native species richness at four sites and negatively related at one. The 10 most frequently occurring and abundant exotic plant species in the prairie fragments were cool‐season, or C3, species, in contrast to the native plant community, which was dominated by warm‐season, or C4, species. This suggests that timing is important to the success of exotic species in the tallgrass prairie. Our study indicates that some small fragments of tallgrass prairie are relatively intact and should not be overlooked as long‐term refuges for prairie species, sources of genetic variability, and material for restoration.