The donor's blood type must be determined if the blood will be used for transfusions. The collecting agency usually identifies whether the blood is type A, B, AB, or O and the donor's Rh (D) type and will screen for antibodies to less common antigens. More testing, including a crossmatch, is usually done before a transfusion. Group O is often cited as the "universal donor" but this only refers to red cell transfusions. For plasma transfusions the system is reversed and AB is the universal donor type. Most blood is tested for diseases, including some STDs. The tests used are high-sensitivity screening tests and no actual diagnosis is made. Some of the test results are later found to be false positives using more specific testing. False negatives are rare, but donors are discouraged from using blood donation for the purpose of anonymous STD screening because a false negative could mean a contaminated unit. The blood is usually discarded if these tests are positive, but there are some exceptions, such as autologous donations. The donor is generally notified of the test result.

The donor is also examined and asked specific questions about their medical history to make sure that donating blood isn't hazardous to their health. The donor's hematocrit or haemoglobin level is tested to make sure that the loss of blood will not make them anaemic, and this check is the most common reason that a donor is ineligible. Pulse, blood pressure, and body temperature are also evaluated. Elderly donors are sometimes also deferred on age alone because of health concerns.