Coronary artery and peripheral vascular disease are associated with significant morbidity and mortality. In these patients, surgical intervention including small diameter bypass grafting with autologous veins or arteries is a common treatment. However, many patients lack suitable autologous vessels, either because these vessels are diseased themselves or because of previous surgery, and in these cases, synthetic grafts are often used. Unfortunately, many of these grafts fail because of the low number of endothelial cells and the proportion of the endothelialised surface remaining after exposure to flow, which results in acute thrombosis and subsequent occlusion of the vessel. At the University of Manchester, we are developing small calibre vascular grafts for coronary or peripheral bypass and vascular access grafts for haemodialysis. These grafts are based on electrostatically spun polyurethane and polycaprolactone with controlled porosity and biodegradability and are coated with specific vascular matrix molecules to regulate cell adhesion, migration, and growth factor bioavailability. This talk will focus on the approaches we are using to improve both the initial adhesion of endothelial cells to the graft surface and the retention of these cells to this surface following restoration of flow. Our studies have revealed significant new insights into the biology of endothelial cell attachment to surfaces coated with specific vascular matrix molecules, with important implications for the design of the next generation of vascular grafts.