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Massive splenic infarction (MSI) is a rare complication of sickle cell disease, as the spleen generally atrophies within the first few years of life. We report a case of MSI in a 12-year-old boy with homozygous sickle cell anemia (Hb SS) whose chronic transfusion therapy resulted in hypersplenism. The occurrence of a complicated MSI in our patient should perhaps further encourage elective splenectomy in such patients, despite known potential perioperative complications and postsplenectomy risks of infection and thrombosis.