Vein grafts are initially thin-walled vessels that must undergo wall thickening to resist increased stress in the arterial circulation. The neointimal hyperplasia that produces this thickening, however, involves the proliferation of activated smooth muscle cells that create a substrate for accelerated atherosclerosis and subsequent graft occlusion. Blocking neointimal hyperplasia, as we have done using an E2F decoy oligonucleotide, induces an adaptive hypertrophic thickening of the medial layer of the vessel, yielding hemodynamic stability without increased susceptibility to atherosclerotic disease.