Reconstructing ancestral characters on a phylogeny is an arduous task because the ob-served states at the tips of the tree correspond to a single realization of the underlying evolutionary process. Recently, it was proposed that ancestral traits can be indirectly estimated with the help of molecular data, based on the fact that life history traits in˛u-ence substitution rates. Here we challenge these new approaches in the Cetartiodactyla, a clade of large mammals which, according to paleontology, derive from small ancestors. Analysing transcriptome data in 41 species, of which 22 were newly sequenced, we pro-vide a dated phylogeny of the Cetartiodactyla and report a signi˝cant e˙ect of body mass on the overall substitution rate, the synonymous vs. non-synonymous substitu-tion rate and the dynamics of GC-content. Our molecular comparative analysis points to-ward relatively small Cetartiodactyla ancestors, in agreement with the fossil record, even though our data set almost exclusively consists of large species. This analysis demon-strates the potential of phylogenomic methods for ancestral trait reconstruction and gives credit to recent suggestions that the ancestor to placental mammals was a rela-tively large and long-lived animal.