The family Ephemerellidae includes 20 genera and approximately 300 species worldwide. Little is understood about the phylogenetic placement of this family relative to other mayfly groups, and relationships within Ephemerellidae have yet to be formally investigated. The objectives of this study are to (1) determine the placement of Ephemerellidae among the other ephemerelloid mayfly families; (2) investigate intergeneric relationships within Ephemerellidae; and (3) use this topology to decipher evolutionary trends including modifications of the larval gills. We generated a robust phylogeny based on 124 morphological characters and six genes (18S rDNA, 28S rDNA, 12S rDNA, 16S rDNA, and Histone 3;=6255 bp ) from 50+ taxa for the majority of ephemerellid genera and ephemerelloid families. Our topology supports the monophyly of the superfamilies Ephemerelloidea and Caenoidea and the families Ephemerellidae, Teloganodidae, Tricorythidae, and Leptohyphidae.