It has been proved that high molecular weight hyaluronic acid (HMW-HA, 1 × 106 Da) micro-strips on titanium (Ti) surface can elongate the human vascular endothelial cell (EC) morphology, subsequently enhance endothelial extracellular matrix (ECM) deposition in our previous work. The HMW-HA micro-strips were anticipated to possess good hemocompatibility and EC compatibility simultaneously. However, the single HMW-HA micro-strips on Ti substrate showed bad hemocompatibility. To solve this problem, a method combining HA micro-pattern and EC decellularization was developed, and the endothelial extracellular matrix layer on the HA micro-pattern (ECM/HAP) showed excellent hemocompatibility and endothelial progenitor cells (EPCs) compatibility (cell number: 14.3 ± 0.5 × 105 cells/cm2 > 2.2 ± 0.7 × 105 cells/cm2 on ECM/TiOH, 7.5 ± 1.3 × 105 cells/cm2 on TiOH, 3.4 ± 0.9 × 105 cells/cm2 on TiOH/HAP and 3.6 ± 1.2 × 105 cells/cm2 on Ti). We also found that the ECM/HAP coating could significantly inhibit the excessive proliferation of smooth muscle cells (SMCs) (cck-8 absorption: 0.25 ± 0.06 < 1.18 ± 0.09 A.U. on ECM/TiOH, 0.87 ± 0.15 A.U. on TiOH and 1.55 ± 0.11 A.U. on Ti) and the attachment of macrophages (cell number: 1.3 ± 0.1 × 103 < 9.2 ± 1.5 × 103 cells/cm2 on ECM/TiOH, 8.8 ± 0.3 × 103 cells/cm2 on TiOH, 7.3 ± 0.7 × 103 cells/cm2 on TiOH/HAP and 9.6 ± 0.9 × 103 cells/cm2 on Ti in 12 h). These data suggest that the multifunctional ECM/HAP coating can be used to build the bionic human endothelial ECM on the biomaterials surface, which might provide a potential and effective method for surface modification of cardiovascular devices.