A blood transfusion is safest when the blood type of the transfused blood matches the recipient's blood type and Rh status (in other words, the blood types are compatible). Therefore, before a transfusion, blood banks do a test called a type and cross-match on the donor's and the recipient's blood. This test minimizes the chance of a dangerous or possibly fatal reaction.

In addition, the recipient's blood is checked for certain antibodies to red blood cells. Such antibodies can cause a reaction to transfused blood.

However, in an emergency, anyone can receive type O red blood cells. Thus, people with type O blood are known as universal donors. People with type AB blood can receive red blood cells from a donor of any blood type and are known as universal recipients.

Recipients whose blood is Rh-negative must receive blood from Rh-negative donors (except in life-threatening emergencies), but recipients whose blood is Rh-positive may receive Rh-positive or Rh-negative blood.