This manuscript consolidates 25 years of interdisciplinary research and clinical advancement in optimizing patient outcomes following osteochondral allograft (OCA) transplantation. In this manuscript, we detail the results of over 1500 OCA procedures and 115 research publications, integrating hypothesis-driven basic science and translational research with clinical outcomes data. The study highlights groundbreaking advancements, including:​ Innovations in fresh OCA preservation techniques that extend graft viability;​ Minimization of immunogenic, thermal, and impaction effects to enhance graft integration and durability;​ Cutting-edge methods for donor-recipient topographic matching, supported by 3D modeling;​ Evolution of the surgical technique, including the development of orthobiologic approaches to optimize outcomes;​ Evaluating long-term clinical outcomes and the effect of concomitant procedures;​ Decision-support algorithms that improve patient selection and surgical planning using machine learning tools. This manuscript illustrates the evolution of OCA transplantation into a reproducible, globally adopted technique for cartilage restoration. By merging basic science, translational insights, and clinical expertise, we redefine and improve the standards of graft handling, surgical technique, and clinical outcomes. The resulting data-driven guidelines and decision-support tools set a foundation for advancing the field, improving accessibility and patient selection, and enhancing patient outcomes worldwide.