The sub-continent of West Africa is made up of 16 countries: Benin, Burkina Faso, Cape Verde, Ghana, Guinea, Guinea-Bissau, Ivory Coast, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, The Gambia and Togo. As of 2018, the population of the sub-continent was estimated at about 381 million. The main challenge associated with blood transfusion service delivery across the sub-region concerns adequacy and safety. In this chapter, we highlighted the challenges associated with the delivery of a quality blood transfusion service in countries in the sub-region including: implementation of component therapy rather than whole blood transfusion, effective cold chain management of blood and blood products, alloimmunization prevention, implementation of column agglutination and automation rather than the convention manual tube method in blood transfusion testing, effective management of major haemorrhage, optimization of screening for transfusion transmissible infections, optimizing blood donation, implementation of universal leucodepletion of blood and blood products, effective management of transfusion-dependent patients, pre-operative planning and management of surgical patients, management of Rhesus D negative pregnancy and women with clinically significant alloantibodies, implementation of haemovigilance system, implementation of alternatives to allogenic blood, availability and use of specialized blood products, optimizing safe blood donation, enhancing blood transfusion safety, operating a quality management system-based blood transfusion service and implementation of non-invasive cell-free foetal DNA testing. There is the urgent need for the implementation of evidence-based best practices in blood transfusion service delivery across the sub-region to allow for excellent, safe, adequate and timely blood transfusion service delivery across the sub-region.