Coronary artery disease is a great threat to human health and is the leading killer worldwide. Percutaneous coronary intervention is the most effective therapy; however, thrombus, and restenosis caused by endothelium injury continue to be problematic after treatment. It is widely accepted that surface biofunctional modification to improve blood compatibility and accelerate endothelialization may be an effective approach to prevent the occurrence of adverse cardiac events. In this study, novel VEGF-loaded heparin/poly-L-lysine (Hep/PLL) particles were developed and immobilized on a dopamine coated titanium surface. The size, distribution, zeta potential, and morphology of the prepared particles were subsequently characterized. The influence of changes in the surface physicochemical properties after particle immobilization was assessed for blood compatibility and cytocompatibility. Surface-modified VEGF-loaded particles significantly inhibited platelet adhesion and activation and were effective in promoting the proliferation and survival of endothelial progenitor cells and endothelial cells. Moreover, Hep/PLL particles were also beneficial for controlling the long-term release of VEGF, which may facilitate endothelium regeneration. In conclusion, VEGF-loaded Hep/PLL particles were successfully immobilized on the Ti surface, and the biocompatibility was significantly improved. This study demonstrates a potential application for the multifunctional modification of stent surfaces for clinical use.