© 2016 by The Southern Medical Association. Objectives Alloantibody formation secondary to transfusion in patients with sickle cell disease (SCD) is a well-known phenomenon. Pretransfusion testing (eg, "antibody screening") protects patients from receiving incompatible red blood cell transfusions. Because alloantibodies have a tendency to evanesce (ie, become undetectable over time), however, this phenomenon puts patients at risk of a delayed hemolytic transfusion reaction or even acute hemolysis. Methods We evaluated the records of 71 patients with SCD with alloantibodies detected during a 2-year period to describe their most common specificities and their rate of evanescence. Results We found that 81% of patients had at least one antibody that was undetectable during the study period; therefore, if patients were transfused with antigen-positive units at a facility that was unaware of their antibody history, life-threatening hemolysis could develop. Conclusions Evanescence is a real risk for patients with SCD, and national/regional databases of alloantibodies should be considered a priority.