A systematic update of the species of Proterotheriidae (Litopterna) from the “Mesopotamiense” of Entre Rios Province (Argentina) is performed, and their phylogenetic relationships with other members of the family are tested. Brachytherium cuspidatum Ameghino is validated (considered nomen dubium hitherto) and a sexual dimorphism is proposed for this species. This idea is based on metric, but not morphological, differences among the specimens included in it, which is supported by a discriminant analysis. Neobrachytherium ameghinoi Soria and Proterotherium cervioides Ameghino are also valid, and Epitherium? eversus (Ameghino) is assigned to the genus Diadiaphorus. Detailed descriptions of the specimens are presented for each taxon, and their diagnosis are revised.