Objective: The ideal vascular graft for use in children with congenital heart disease should not only be biocompatible and nonthrombogenic and present no infectious risk, but ideally it should grow at the same rate as the recipient. Methods: We have tested autologous small intestine submucosa as a superior vena cava interposition graft in 11 piglets. The grafts were prepared from segments of jejunum, rendered nonthrombogenic by heparin bonding. The superior vena cava from the level of the azygos vein to the superior vena cava-right atrial junction was replaced. Results: One early and 1 late death were not related to the graft material. At 90 days, the weight of the 9 survivors increased by 630%, from a mean of 10.3 ± 2.0 kg to a mean of 59.2 ± 16.7 kg (P < .001). The grafts increased in circumference by 184%, from a mean of 36.8 ± 4.4 mm to a mean of 61.4 ± 12.1 mm (P < .001) at late follow-up. Their length increased by 147%, from a mean of 9.9 ± 2.1 mm at implantation to a mean of 15.8 ± 5.5 mm at explantation (P = .002). At the time of explantation, all 11 grafts were patent and free of thrombus. Cavograms showed no anastomotic stricture or aneurysm formation in 7 of 9 cases. The luminal surface of all grafts was smooth, shiny, and indistinguishable from that of the native cava. Light microscopy showed a loosely textured collagen framework, with a dense capillary network and complete luminal coverage by a single, continuous cell layer displaying the ultrastructural features characteristic of endothelial cells. Conclusion: Small intestine submucosa provides a collagen framework that becomes remodeled, grows, and acquires a nonthrombogenic endothelial lining. This makes it potentially well suited as a cardiovascular substitute in children.