Thrombus, hyperplasia, and inflammation are constant threats and challenges for long-term application of cardiovascular implants. Surface endothelialization has been considered as the preferable strategy to solve these problems because of the physiological functions gained from the regenerated endothelial layers covering the implants. Thus, a surface with strong multi-functions including anti-coagulation, anti-hyperplasia, anti-inflammation, and pro-endothelialization is ideal for cardiovascular implants. Herein, we developed a novel coating by conjugating chondroitin sulfate (CS) onto an amine-rich copolymerized film of polydopamine (PDA) and hexamethylenediamine (HD), with the aim of directing the vascular cell fate. The PDA/HD-CS coating exhibited a remarkable suppression of platelet activation/aggregation and thrombosis under a blood flow of 15 dyn cm-2. Inhibition upon proliferation of vascular smooth muscle cells and attachment of macrophages were also observed on this coating. In addition, the PDA/HD-CS coating was compatible with the vascular endothelial cells, suggesting a strong pro-endothelialized function. Further in vivo tests indicated that contractile smooth muscle cells and M2 macrophages regulated by PDA/HD-CS may be involved in the regeneration of the endothelial layer. In summary, this research may support potential applications for surface modification of cardiovascular implants to achieve improved multi-functions.