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In this report, the effects of RFGD coatings of tetraglyme on the lumenal surface of PE tubing on \u0393<jats:sub>Fg<\/jats:sub> and on blood interactions both <jats:italic>in vitro<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic> are described. \u0393<jats:sub>Fg<\/jats:sub> on the tetraglyme\u2010coated PE tubing was reduced to the desired ultralow level (&lt;10 ng\/cm<jats:sup>2<\/jats:sup>), and we also observed a significant decrease in adsorption of von Willebrand's factor. <jats:italic>In vitro<\/jats:italic> platelet adhesion from washed platelet suspensions, platelet rich plasma, or whole blood to tetraglyme\u2010coated PE tubing was decreased compared to PE, polyurethane, or silicone rubber tubes. In addition, thrombin generation by platelets adherent to tetraglyme\u2010coated PE was also much less than by platelets adherent to PE. When inserted in an <jats:italic>ex vivo<\/jats:italic> carotid artery\u2010carotid artery shunt in sheep, the RFGD tetraglyme\u2010coated PE exhibited a very low number of adherent platelets compared to heparin\u2010coated, chromic acid\u2010etched, or plain PE. The RFGD tetraglyme\u2010coated PE tubes exhibited high protein and platelet resistance <jats:italic>in vitro,<\/jats:italic> and high platelet resistance <jats:italic>ex vivo<\/jats:italic>. The improved hemocompatibility is attributed to the unique chemical structure of RFGD tetraglyme that makes it highly protein resistant. \u00a9 2006 Wiley Periodicals, Inc. 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