ObjectivesAcute hemolytic transfusion reaction (AHTR) due to ABO-incompatible erythrocyte concentrate (EC) is one of the most catastrophic complications of transfusion. Since the hemolysis is intravascular; hemoglobinemia and hemoglobinuria result in disseminated intravascular coagulation (DIC), acute renal failure, shock, and sometimes death. BackgroundTreatment of AHTR is mostly supportive measures. Today there are no clear suggestions about plasma exchange (PE) in these patients. Methods/MaterialsHere we report our experience with six patients diagnosed with AHTR due to ABO-incompatible EC transfusion. ResultsWe performed PE in 5 of these patients. Although all of our patients were geriatric and most of them had significant comorbidities four out of five patients recovered without an incident. ConclusionAlthough PE is considered a last-chance treatment when other measures fail in the literature, our experience above indicates that it must be evaluated in every patient with AHTR early in the course. If the patient has cardiac and renal comorbidities, large volume EC is transfused, DAT is negative, plasma color is red and there is macroscopic hemoglobinuria, we suggest performing PE.