BackgroundSouth Africa has a population of 52 million people and is classified as a Middle Human Development Index (HDI) Country. Up until 1994, the majority Black population lived under discriminatory apartheid laws with resulting in significant socio‐economic disparities between the various population groups. The health system is two tier with Government funding health care in the public sector and medical insurance schemes funding health care in the private sector for those who can afford it. Fiscal allocation for health care in the public sector has been averaging at about 8·5% of the country's gross domestic product (GDP) and is utilized by 84% of the population as the majority of the population cannot afford medical insurance. There is inadequate value contribution due to high disease burden, increasing demand for services from previously disadvantaged groups and inefficiencies in service delivery. The blood services operate on a fee‐for‐service basis supplying about 60% of blood to public sector hospitals and about 40% to private health facilities. The South African National blood service (SANBS) supplies blood and blood products to 88% of the population in eight of the nine provinces and the Western Province Blood Transfusion Service (WPBTS) which operates independently in the Western Cape Province supplies the remaining 12%. Both blood services operate on a ‘vein to vein’ basis managing blood collections from 100% voluntary non‐remunerated donors, processing whole blood into various components, testing for viral markers and cross matching and issuing blood products to doctors on request. SANBS was formed as a National Blood Service in 2001 as a result of the amalgamation of 6 regional blood service organizations. The mission of SANBS is ‘to provide all patients with sufficient, safe, quality blood products and related medical services in a sustainable manner’. Blood safety and sufficiency are the most critical objectives of both blood establishments (BEs).AimTo present historical developments and achievements of SANBS in pursuit of its mandate over the last 12 years. The objective is to share outcomes of various strategies that enabled and strengthened delivery in the South African resource‐constrained environment and challenging socio‐economic context.MethodsA review of the strategic plans, governance framework, operational service delivery and efficiency, human resource management, financial efficiency and stakeholder management was performed to highlight the strategy, challenges and successes of organizing a national blood service.ResultsDespite significant socio‐economic challenges and limited resources SANBS has managed to effectively provide a low risk and sustainable blood supply to the patients that it serves.