Autologous fat transplantation is plagued by an unpredictable and often significant degree of graft loss. AdE4+ endothelial cells (ECs), are human endothelial cells that have been transduced with the E4ORF1 region of human adenovirus Type 5, resulting in long-term preservation of EC proliferation and angiogenic capability without immortalization. We hypothesized that AdE4+ EC-enriched fat grafts would demonstrate improved volume retention secondary to enhanced angiogenesis. Three experimental groups were prepared by admixing 400µL of patient lipoaspirate with 100µL of AdE4+ EC suspensions (“high” AdE4+ EC concentration-enriched (5 x 106/mL), “low” AdE4+ EC concentration-enriched (1.25 x 106/mL) or PBS), and injected subcutaneously into the bilateral dorsa of nude mice. Fat transplants were explanted at 90 and 180 days for volumetric and histologic analyses. After both 90 and 180 days, AdE4+ EC-enriched fat grafts showed greater mean volume preservation compared to control grafts (p < 0.05). Regions of focal necrosis were only noticed in low AdE4+ EC concentration-enriched and control groups after 180 days. Histologic analysis demonstrated the presence of healthy adipocytes in all AdE4+ EC-enriched fat grafts in which both human and host ECs were evident after 90 and 180 days. AdE4+ EC enrichment improved fat graft volume preservation and vascularization in this murine xenograft model. Though further study is warranted, AdE4+ endothelial cells demonstrate promise as a potential off-the-shelf adjunct for improving the volume, quality, and consistency of fat engraftment.