In coronary artery bypass graft interventions, luminal thrombosis is one of the greatest challenges for polymeric grafts with a luminal diameter less than 4 mm. Previously, we reported the fabrication of a highly porous micro/nanofibrous electrospun scaffold and demonstrated the excellent biocompatibility of the scaffolding materials with human endothelial cells. In this study, we explored the engineering of an antithrombotic layer on the scaffold's lumen within 48 h, using peripheral blood-derived porcine endothelial progentior cells (EPC). Flow cytometric results showed that they were CD31 - but highly CD34+ and CD105+, suggesting the primitive nature of these freshly isolated EPC. The vast majority of EPC readily took up low density lipoprotein, confirming their endothelial phenotype. These EPC also exhibited a strong proliferation capacity on the scaffold for up to 11 days. A confluent layer could be easily engineered within 24 h, which successfully prevented platelet adhesion, a critical step in the cascade of thrombotic events. We concluded that this scaffold could afford a convenient means for the regeneration of a functional cardiovascular endothelium shortly after implantation. © 2011 Wiley Periodicals, Inc.