The oleander aphid, Aphis nerii Boyer de Fonscolombe, feeds on milkweeds in the Apocynaceae family. In Kentucky, A. nerii colonizes several common Asclepias species and honeyvine milkweed, Cynanchum laeve (Michaux). Previous studies investigating whether and how host plant characteristics influence A. nerii fitness have produced conflicting results. Our observations suggested that A. nerii more readily colonized C. laeve than Asclepias species. We hypothesized that aphid fitness differed among host plant species having different characteristics, and specifically, that A. nerii performance would be greatest on host plants having low cardenolide concentrations and few physical defenses. Physical and chemical characteristics were measured on C. laeve and three Asclepias species. Laboratory and field experiments were conducted to compare A. nerii performance among these four milkweed species in the absence of natural enemies. Changes in aphid densities over time were examined in the presence of natural enemies. Plant characteristics and aphid performance were found to differ among milkweed species. In the absence of natural enemies, A. nerii performance was best on C. laeve. When exposed to natural enemies, A. nerii densities remained higher on A. incarnata and C. laeve than on A. syriaca and A. tuberosa. Physical differences between C. laeve, a vining milkweed, and tested Asclepias species may increase suitability of honeyvine milkweed for A. nerii colonization. Our results suggest that C. laeve may rely more on tolerance and less on nonpreference or antibiosis resistance to herbivores.