Heparin-like polymers are promising synthetic materials with biological functionalities, such as anticoagulant ability, growth factor binding to regulate cellular functions, and inflammation mediation, similar to heparin. The biocompatibility of heparin-like polymers with well-defined chemical structures has inspired many researchers to design heparin-like surfaces to explore their biological applications. The concept of the recombination of functional heparin structural units (sulfonate- and glyco-containing units) was proven to be successful in designing heparin-mimicking surfaces. However, besides surface structural units, topographic patterning is also an important contributor to the biological activity of the surfaces modified with heparin-like polymers. In this work, both surface structural units and topographic patterning were taken into account to investigate the vascular cell behaviors on the silicone surfaces. A facile method for the production of patterned bromine-containing polydimethylsiloxane surface (PDMS-Br) was developed from a one-step multicomponent thermocuring procedure and replica molding using a nanohole-arrayed silicon template. Different structural units of heparin-like polymers, i.e. homopolymer of sulfonate-containing sodium 4-vinylbenzenesulfonate (pSS), homopolymer of glyco-containing 2-(methacrylamido)glucopyranose (pMAG), and copolymers of MAG and SS (pSG), were then introduced on the flat and patterned PDMS-Br surface using visible light-induced graft polymerization. For the flat surfaces, compared with the PDMS-Br surface, pSS-grafted and pSG-grafted surfaces significantly increased cell densities of both human umbilical vein endothelial cells (HUVECs) and human umbilical vein smooth muscle cells (HUVSMCs), indicating that they are “vascular cell-friendly”. In contrast, the pMAG-grafted surface showed decreased cell attachment of both HUVECs and HUVSMCs, indicating that the pMAG-grafted surface is “vascular cell-resistant”. Moreover, surface topographic patterning enhanced the cell responses to the corresponding flat surfaces. That is to say, surface patterning can make the “vascular cell-friendly” surface still friendly, and the “vascular cell-resistant” surface much more resistant. The combination of surface structural units and topographic patterning shows promise in the preparation of new heparin-like surfaces with improved cell compatibility that is suitable for blood-compatible biomaterials.