Summary: Decorin (DCN) is an important small leucine-rich proteoglycan present in the extracellular matrix (ECM) of many organs and tissues. Endothelial progenitor cells (EPCs) are able to interact with the surrounding ECM and bind to molecules such as DCN. Here, we recombinantly produced full-length human DCN under good laboratory practice (GLP) conditions, and after detailed immunological characterization, we investigated its potential to attract murine and human EPCs (mEPCs and hECFCs). Electrospun polymeric scaffolds were coated with DCN or stromal cell-derived factor-1 (SDF-1α) and were then dynamically cultured with both cell types. Cell viability was assessed via imaging flow cytometry. The number of captured cells was counted and compared with the non-coated controls. To characterize cell-scaffold interactions, immunofluorescence staining and scanning electron microscopy analyses were performed. We identified that DCN reduced T cell responses and attracted innate immune cells, which are responsible for ECM remodeling. A significantly higher number of EPCs attached on DCN- and SDF-1α-coated scaffolds, when compared with the uncoated controls. Interestingly, DCN showed a higher attractant effect on hECFCs than SDF-1α. Here, we successfully demonstrated DCN as promising EPC-attracting coating, which is particularily interesting when aiming to generate off-the-shelf biomaterials with the potential of in vivo cell seeding.