Background: The production of a small-diameter vascular graft (d<3 mm), utilizing state-of-the-art tissue engineering approaches, currently represents a major challenge in vessel microsurgery. Cardiovasular disease (CVD) affects more than 18 million people, worldwide. Therapeutic options in bypass surgery include the use of autologous grafts, such as the saphenous vein, or synthetic vascular grafts. However, both approaches present unfortunate events, limiting the lifespan of the implanted graft, thus requiring a new replacement surgery. Therefore, the production of vascular grafts utilizing decellularized human umbilical arteries may represent an alternative strategy in the treatment of CVD. Moreover, the efficient combination of the produced vascular graft with the host’s cells may result in the production of a fully histocompatible conduit, thus increasing the lifespan of the implant. For this purpose, we assessed the production of histocompatible vascular grafts obtained from decellularized human umbilical arteries (hUAs), which is the primary aim of this study. Methods: HUAs were decellularized using CHAPS and SDS detergents. The total hydroxyproline, sulphated glycosaminoglycans (sGAGs), and DNA content were quantified. Human endothelial cells (ECs) and smooth muscle cells (SMCs) were seeded in the decellularized hUAs. Typing of the Human Leucocyte Antigens (HLAs) was performed in hUAs both prior to and after the decellularization, as well as in seeded cellular populations. Results: Decellularized hUAs were characterized by the proper preservation of tissue architecture. Total hydroxyproline content was preserved, although sGAGs and DNA presented a statistically significant reduction. HLA typing only confirmed the presence of the seeded ECs and SMCs in the produced vascular grafts, further indicating the successful production of a histocompatible graft. Conclusion: The results of this study support the efficient production of histocompatible human vascular grafts. Based on the most frequent regional HLAs, a bank with histocompatible vessel grafts could be established, bringing personalized medicine a step closer to clinical utility.