New discoveries of numerous fossil femora from giant caviomorph rodents from the Miocene of Venezuela and a specimen of aMiocene giant rodent from Trinidad in the collections of the Naturhistorisches Museum in Basel made possible the first examination of taxonomic, ontogenetic, and functional variation in these animals. We provide comparisons of femoral shape, metrics, and growth (epiphyseal closure), finding that four morphotypes are distinguishable based largely on degrees of robustness or gracility. This indicates that the diversity of giant caviomorphs was larger than previously known; Phoberomys pattersoni was not the only giant caviomorph that inhabited the Miocene of the northern Neotropics. The study of cortical cross-sectional area of fossils serves to estimate the body mass for two giant caviomorphs at 420–580 kg. The first description of patterns of bone microstructure in three fossil giant caviomorph femora reveals similarities to extant rodents: absence of Haversian tissue and presence of layers of lamellar followed by reticular-like bone.