Here, we report the differential effects on cellular ingrowth and healing caused by varying the mternodal distance (IND) of polytetrafluoroethylene (PTFE) grafts. In addition, we examined whether cellular ingrowth could be enhanced by an additional source of endothelial cells. Both carotid arteries of greyhound dogs were replaced with 5-cm lengths of 4-mm-diameter PTFE grafts of varying IND (30, 40, 60 μm). The histologic characteristics of anastomotic and midgraft segments of grafts wrapped with autologous vein graft as a source of endothehal cells were compared to the contralateral unwrapped graft of identical IND. At five weeks the grafts were excised and examined histologically and the in vivo IND, cellular and microvessel ingrowth, and endothelialization of the luminal surface quantitated. All 30 μm grafts (N = 8) were occluded by anastomotic pannus ingrowth (PI). The anastomoses of 40 and 60 μm grafts were characterized by either intimal hyperplasia (IH) (N = 10) or healing with minimal intimal thickening (H) (N = 4). The mean reduction in IND at anastomoses was 68 to 75% for all grafts whereas midgraft IND was unaffected. The mean IND at anastomoses with PI was 7.0 ± 1.5 μm, IH 12.0 ± 2.5 μm, and 19.0 ± 2.0 μm for healed anastomoses. Midgraft cellular ingrowth was greater than that observed near anastomoses and varied with IND. The application of a vein wrap enhanced cellular and microvessel ingrowth and endothelialization of 40 and 60 μm grafts. These data suggest that alterations in PTFE ultrastructure likely resulting from surgical manipulation during implantation may adversely influence anastomotic healing.