Milosaurus mccordi was described in 1970 as a large, pelycosaurian-grade synapsid from the latest Carboniferous of Illinois but has since received little attention. Here, the holotype and referred material of Milosaurus are reexamined and incorporated into a phylogenetic analysis. Milosaurus is resolved within Haptodontiformes, sharing with this clade a posterodorsally expanded ischium and a calcaneum with greater length than width. The more plesiomorphic ischium indicates a basal position within this clade. Most of the referred material shows very little overlap with the holotype and so most was not included in the cladistic analysis. However, what was originally described as a dorsal rib is here judged to be a femur that shares a highly distinctive morphology with the holotype. With its mass estimated as 41 kg, Milosaurus represents one of the largest Carboniferous synapsids. Large size evolved at least twice independently in Haptodontiformes during the Pennsylvanian: once in Sphenacodontidae and once in Edaphosauridae. Using phylogenetic comparative methods, Milosaurus is found to have evolved a large size independently of these two clades. As one of the largest Carboniferous amniotes, and the outgroup to one of the most diverse Paleozoic synapsid lineages, Milosaurus represents a crucial taxon for understanding early terrestrial ecosystems.