Building on the successful military experience, interest has been rekindled in transfusing whole blood (WB) early in the resuscitation of traumatically injured civilians, often before their ABO group is known. WB efficiently provides treatment for shock and coagulopathy, as well as platelet hemostatic function, to patients losing large volumes of blood. Unlike group O uncrossmatched red blood cells (RBCs), group O WB contains a substantial amount of plasma, which is incompatible with the RBCs of all non–group O recipients. Thus, when implementing a WB program, it is important to decide how to mitigate the risk of immune-mediated hemolysis. Other questions that a hospital needs to answer before implementing a WB program include determining which patients will be eligible for this product, how many units eligible patients can receive, for how long it should be stored and under what conditions, and how to monitor for adverse events. The donor center needs to consider if the WB should be leukoreduced, how to comply with the AABB's transfusion-related acute lung injury risk mitigation standard, and into which storage solution it should be collected. This report describes the multidisciplinary approach taken to implementing a civilian WB program at a multihospital health care system in the United States.