Background: 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 biological performance and biomechanical characteristics of this graft. Methods: Heparin-sirolimus (HS) or heparin-sirolimus-vascular endothealial growth factor (HSV) grafts were manufactured for this study. Heparin (40 U) was embedded in the microstructure of the graft for early elution from the graft wall. Heparin (100 U) and sirolimus (450 μg) were incorporated into the macrostructure of the graft for late elution. Vascular endothelial growth factor was also embedded in the microstructure of the graft. Both grafts (3.6 mm internal diameter, 24 mm length) were implanted into the abdominal aortas of rabbits (n = 36) to compare with heparin-alone (H) grafts (n = 9). At 4 hours, 1 day, and 1, 2, and 4 weeks after surgery, the grafts were removed for histologic, immunohistochemical, and biomechanical evaluations. Results: The patency rate of all grafts was 100% at each time point. None of grafts had stenosis after surgery. Endothelial cells were observed at 4 weeks after surgery in the HS, HSV, and H grafts. Although there was no significant difference of neointima thickness among the HS, HSV, and H grafts (136 ± 75, 93 ± 64, and 125 ± 90 μm; p = 0.08), the H grafts did have more cellular infiltration in the graft than the HS or HSV grafts. There was neocapillary formation inside the graft wall at 4 weeks in all grafts. The graft macrostructure was unchanged based on biomechanical evaluation 4 weeks after surgery. Conclusions: A unique drug-eluting graft had excellent patency at 1 month and may encourage luminal endothelialization without excessive intimal hyperplasia. Although vascular endothelial growth factor did not improve intimal formation, cell infiltration, or vascularization, sirolimus might inhibit cell proliferation. Further long-term study would need to evaluate the efficacy of impregnated sirolimus.