The development of an ideal small-diameter conduit for use in vascular bypass surgery has yet to be achieved. The ongoing innovation in biomaterial design generates novel conduits that require preclinical assessment in vivo, and a number of animal models have been used for this purpose. This article examines the rationale behind animal models used in the assessment of small-diameter vascular conduits encompassing the commonly used species: baboons, sheep, pigs, dogs, rabbits, and rodents. Studies on the comparative hematology for these species relative to humans are summarized, and the hydrodynamic values for common implant locations are also compared. The large- and small-animal models are then explored, highlighting the characteristics of each that determine their relative utility in the assessment of vascular conduits. Where possible, the performance of expanded polytetrafluoroethylene is given in each animal and in each location to allow direct comparisons between species. New challenges in animal modeling are outlined for the assessment of tissue-engineered graft designs. Finally, recommendations are given for the selection of animal models for the assessment of future vascular conduits.