<jats:p> <jats:italic>Background</jats:italic> —Clinical trials show that larger immediate postdeployment stent diameters provide greater ultimate luminal size, whereas animal data show that arterial injury and stent design determine late neointimal thickening. At deployment, a stent stretches a vessel, imposing a cross-sectional polygonal luminal shape that depends on the stent design, with each strut serving as a vertex. We asked whether this design-dependent postdeployment luminal geometry affects late neointimal thickening independently of the extent of strut-induced injury. </jats:p> <jats:p> <jats:italic>Methods and Results</jats:italic> —Stainless steel stents of 3 different configurations were implanted in rabbit iliac arteries for 3 or 28 days. Stents designed with 12 struts per cross section had 50% to 60% less mural thrombus and 2-fold less neointimal area than identical stents with only 8 struts per cross section. Sequential histological sectioning of individual stents showed that immediate postdeployment luminal geometry and subsequent neointimal area varied along the course of each stent subunit. Mathematical modeling of the shape imposed by the stent on the artery predicted late neointimal area, based on the re-creation of a circular vessel lumen within the confines of the initial stent-imposed polygonal luminal shape. </jats:p> <jats:p> <jats:italic>Conclusions</jats:italic> —Immediate postdeployment luminal geometry, dictated by stent design, determines neointimal thickness independently of arterial injury and may be useful for predicting patterns of intimal growth for novel stent designs. </jats:p>