Recent advances in vascular tissue engineering have enabled a paradigm shift from ensuring short-term graft survival to focusing on long-term stability and growth potential. We present the first experimental-computational study of a tissue-engineered vascular graft (TEVG) effectively over the full lifespan of the recipient. We show that grafts implanted within the venous circulation of mice remained patent over 2 years without thrombus, stenosis, or aneurysmal dilatation. Moreover, the gross appearance and mechanical properties of the grafts evolved to be similar to the host vein within 24 weeks, with mean neovessel geometry and properties remaining unchanged thereafter despite a continued turnover of extracellular matrix. Biomechanical diversity manifested after 24 weeks, however, via two subsets of grafts despite all procedures being the same. Computational modeling and associated immunohistological analyses suggested that this diversity likely resulted from a differential ratio of collagen types I and III, with lower I to III ratios promoting grafts having a compliance similar to the native vein. We submit that TEVGs can exhibit the desired long-term mechanobiological stability; hence, we must now focus on evaluating growth potential and optimizing scaffold properties to achieve compliance matching throughout neovessel development.