The evaluation of porcine small intestine submucosa (SIS) in a microsurgical model was conducted using an interpositional graft in the rat femoral artery. The SIS grafts were fabricated from processed porcine material that was wrapped around a glass tube and oversewn longitudinally to produce a tubular structure. Of the 42 animals studied, 7 received grafts of untreated SIS (group I), 7 of the grafts were presoaked (PSH) in heparin (Group II), 7 animals were treated with systemic heparin prior to implantation of PSH‐SIS (group III), 7 animals received SIS grafts crosslinked to heparin (group IV), 7 animals received SIS grafts crosslinked to urokinase (group V), and 7 animals received untreated autologous epigastric vein grafts (group VI). Patency was assessed postoperatively and selected grafts were evaluated by histology. All SIS grafts failed to maintain patency beyond the first postoperative hour. Histologic examination of the thrombosed graft surfaces revealed a smooth luminal surface with a thick layer of attached fibrin and platelets with a central occluding thrombus. The thickness of the induced fibrin layer appears to narrow intraluminal space significantly at the microvascular level. While having excellent success at vessel diameters greater than 3 mm, and in a variety of nonporcine animal models without xenographic rejection, SIS in this model was thrombogenic despite a favorable surface morphology as demonstrated by SEM. Even with use of heparin and urokinase SIS graft thrombosis occurred. © 1994 Wiley‐Liss, Inc.