Many physiologic and pharmacologic studies require long-term vascular access for repeated substance infusion and/or blood sample collection. The study reported here was undertaken to determine whether a functionally active heparin coating would improve long-term patency of venous catheters in rats. Uncoated or coated catheters were surgically placed in the jugular vein, and patency was evaluated twice weekly for a total of 30 days. Culturing of blood and catheters, and histologic examination were performed for all rats. All heparin-coated catheters remained patent for the study duration, with patency defined as ability to infuse saline and withdraw a blood sample. Median patency for uncoated catheters was 17.5 days, with a range of three to 30 days. Histologic evaluation of vessels revealed more advanced and severe lesions in rats with uncoated, compared with coated catheters. Furthermore, uncoated catheters had increased association with bacteremia (3/8), compared with coated (0/9) catheters. Taken together, these results indicate that coating catheters with covalently bound heparin molecules can significantly prolong patency and cause less pathologic damage to the catheterized vessel.