The Republic of Croatia is a global leader in organ donation and transplantation despite having fewer resources and more modest healthcare expenditures than other countries in the European Union. The results of an extensive literature review were combined with expert input in an iterative multi-step data collection and evaluation process designed to assess trends in Croatian organ donation and transplantation and identify key elements, policy changes, and drivers of the system that have contributed to its success. Multiple sources of evidence were used in this study, including primary documents, national and international transplantation reports, and insights from critical informants and content experts. The results highlight several key organizational reforms that have substantially improved the performance of the Croatian transplant program. Our findings emphasize the importance of strong central governance led by an empowered national clinical leader acting under the direct auspices of the Ministry of Health and a comprehensive and progressive national plan. The Croatian transplant system is notable for its integrated approach and efficient manner of managing scarce health resources. Collectively, the results suggest that Croatia has become nearly self-sufficient due to its systematic implementation of the guiding principles for organ donation and transplantation.