South America had an endemic mammalian fauna for much of the Cenozoic, largelyevolved during its long isolation. The predator guild was mainly occupied bymetatherians (Sparassodonta), as well as large terrestrial birds(Phorusrhacidae), agile terrestrial crocodiles (Sebecidae), and giant snakes(Madtsoiidae). Sparassodonta was a diverse clade, recorded from the Paleocene tothe Middle Pliocene, with its acme in the late Early Miocene (Santacrucian Age).In this chapter, we review the paleoecology of the sparassodonts known from theSanta Cruz Formation and include new results obtained by geometric morphometricanalyses. The Santa Cruz Formation contains 11 sparassodont species: sixHathliacynidae (Acyon tricuspidatus,Cladosictis patagonica, Sipalocyon gracilis, Sipalocyon obusta, Pseudonotictispusillus, Perathereutespungens) and five Borhyaenoidea (Prothylacynus patagonicus, Lycopsistorresi, and three Borhyaenidae, Borhyaena tuberata, Acrocyonsectorius, and Arctodictismunizi). These sparassodonts were mainly hypercarnivoresexhibiting different locomotor abilities (from scansorial to terrestrial), and awide range of body masses (from 1 kg to more than 50 kg). The reconstruction ofthe Santacrucian predator guild suggests that there was good ecologicalseparation within the sparassodonts, determined by particular combinations ofbody size, locomotion, and diet. The diversity of sparassodonts recorded in theSanta Cruz Formation (11 species) and in the Estancia La Costa Member (sevenspecies), is similar to that observed in present and past placentalhypercarnivore communities.