Litopterna from fossiliferous exposures of the Santa Cruz Formation (Early-Middle Miocene) along the Río Santa Cruz, Patagonia Argentina, are analyzed and described. In the prospected localities, known as Barrancas Blancas (Estancia Aguada Grande and Estancia Santa Lucía) and Segundas Barrancas Blancas (Estancia Cordón Alto and Estancia El Tordillo), specimens belonging to the families Proterotheriidae and Macraucheniidae were recorded. Within Proterotheriidae, the species Anisolophus australis, A. floweri, Tetramerorhinus lucarius, Te. cingulatum, Thoatherium minusculum and Diadiaphorus majusculus have been identified. Macraucheniidae are scarcer and represented by Theosodon sp. Although the systematics of litopterns of the Santa Cruz Formation requires a review, the new remains from the Río Santa Cruz reported here, as well as others recently recovered from the same unit in the Atlantic coast, will be valuable to clarify the taxonomy of this peculiar group of South American extinct ungulates.