Parsimony analysis of the mitochondrial 12S and 16S rRNA sequences of North American phoxinin taxa indicated the existence of three major clades, the Western Clade, the Creek Chub Clade, and the Open Posterior Myodome Clade. The monophyletic Western Clade identified in this paper contained fewer taxa than that identified by previous authors. This clade contained species restricted to drainages west of the Continental Divide, such asGila, Acrocheilus, Relictus, Eremichthys, Siphateles, Ptychocheilus, Lavinia,andOrthodon,and the wide-ranging genusPhoxinusfound in eastern North America and Eurasia. Within this Western CladePhoxinuswas the basal sister group.Gilawas recognized as a monophyletic group exclusive ofSiphatelesandSnyderichthys,clades traditionally recognized as subgenera ofGila.The genusGilawas most closely related to the genusAcrocheilusand together these formed the sister group to the genusRelictus.These relationships were supported independent of weighting schemes used in analyses. Identification ofPhoxinusas the basal sister taxon of the Western clade implies that other major clades of North American Phoxinins likely have Asian or European relatives.