Objective: A bioengineered microporous polycarbonate-siloxane polyurethane graft has been developed for coronary artery bypass grafting. Biological agents can be impregnated into its absorbable collagen and hyaluronan microstructure and stable macrostructure to promote patency. The objective of this study was to examine the in vivo biological performance and biomechanical characteristics of this graft. Methods: Three types of graft (3.6-mm internal diameter, 24-mm length) were manufactured: heparin alone (H) grafts, heparin and sirolimus (HS) grafts, and grafts without any drug impregnation (C). All H and HS grafts were impregnated with 54 U of heparin in the microstructure for early elution to prevent acute graft thrombosis and 56 U of heparin in the macrostructure to prevent late thrombosis. In addition to the heparin, the HS graft was impregnated with 2.1 mg of sirolimus in the macrostructure for prolonged elution to inhibit intimal hyperplasia. All grafts (3.6-mm internal diameter, 24-mm length) were implanted into the abdominal aortas of rabbits (n = 55). Expanded polytetrafluoroethylene grafts (4.0-mm internal diameter, 24-mm length; n = 7) were implanted as controls. At 1, 3, and 6 months after surgery, the grafts were removed for histologic, scanning electron microscopic, immunohistochemical, and biomechanical evaluations. Results: The patency rate was 100% in the H, HS, and C grafts at each time point. Although the expanded polytetrafluoroethylene grafts were patent at 1 and 3 months after surgery, 1 of 2 grafts (50%) were occluded at 6 months. None of the H or HS grafts had any stenosis or thrombus. Scanning electron microscopic examination proved that endothelial cells propagated smoothly from the anastomotic sites after 6 months in the H and HS grafts in comparison with the expanded polytetrafluoroethylene grafts, which had rare endothelialization. Neointima formation was inhibited in the HS graft compared with the H or C graft at 6 months (123 ± 126 μm vs 206 ± 158 μm or 202 ± 67 μm; P < .05). In addition, the H, HS, and C grafts had greater cellular infiltration inside the graft than the expanded polytetrafluoroethylene grafts. All grafts except the expanded polytetrafluoroethylene graft had marked neocapillary formation 6 months after surgery. The graft compliance between 80 and 120 mm Hg was 6.0% ± 2.5% and 6.2% ± 0.9% at 6 months in the H and HS grafts, respectively. The graft macrostructure was unchanged according to the biomechanical evaluation in the H and HS grafts. Conclusion: A unique drug-eluting graft had excellent patency throughout the 6 months after implantation. The heparin-sirolimus graft encouraged luminal endothelialization without excessive intimal hyperplasia. This graft performed significantly better than the expanded polytetrafluoroethylene graft. This graft has the potential to become an implantable graft for coronary artery bypass grafting.