Inhibition of smooth muscle cell (SMC) proliferation and preservation of a differentiated state are important aspects in the management, avoidance and progression of vascular diseases. An understanding of the interaction between SMCs and the biomaterial involved is essential for a successful implant. In this study, we have developed collagen immobilized nanostructured surfaces with controlled arrays of high aspect ratio nanowires for the growth and maintenance of human aortic SMCs. The nanowire surfaces were fabricated from polycaprolactone and were immobilized with collagen. The objective of this study is to reveal how SMCs interact with collagen immobilized nanostructures. The results indicate significantly higher cellular adhesion on nanostructured and collagen immobilized surfaces; however, SMCs on nanostructured surfaces exhibit a more elongated phenotype. The reduction of MTT was significantly lower on nanowire (NW) and collagen immobilized NW (colNW) surfaces, suggesting that SMCs on nanostructured surfaces may be differentiated and slowly dividing. Scanning electron microscopy results reveal that SMCs on nanostructured surfaces are more elongated and that cells are interacting with the nano-features on the surface. After providing differentiation cues, heavy chain myosin and calponin, specific to a contractile SMC phenotype, are upregulated on collagen immobilized surfaces. These results suggest that nanotopography affects cell adhesion, proliferation, as well as cell elongation, while collagen immobilized surfaces greatly affect cell differentiation.