Abstract: Objective To evaluate the effect of double-filtration plasmapheresis (DFPP) in major ABO-incompatible unrelated allogenic bone marrow transplantation. Methods The red cell antibodies were removed by DFPP in 5 recipients to prevent hemolysis and pure red cell aplasia following major ABO-incompatible unrelated bone marrow transplantation. Results The isohemagglutinin titers of the 5 recipients were below 1:16 after DFPP with only one recipient developed transient mild acute hemolysis. Delayed hemolysis and pure red cell aplasia occurred in none of the cases and all recipients were completely engrafted. Conclusion DFPP can effectively prevent hemolysis and pure red cell aplasia in recipients of unrelated bone marrow transplantation with major ABO-incompatibility.