The session will start with how low titer group O whole blood (LTOWB) has become part of the 21st-century massive transfusion protocol (MTP) of both adult and pediatric trauma and non-trauma settings with a focus on North America. The session will demonstrate how to design and implement an LTOWB program in both the blood center and transfusion service. There will be a discussion on matters important to blood centers, including the use of platelet-sparing leukoreduction filters, what is considered “low titer,” the possibility of manufacturing unused units into components, and recruitment concerns of a dedicated program. Transfusion service logistics will be covered, including availability and wastage. Rh (D) considerations, particularly in women of childbearing age and pediatric patients, will be an area of focus. The use of LTOWB prehospital and in-hospital and effects on patient outcomes will be addressed. The session will conclude with the future directions of LTOWB.