Objective:To explore the clinical manifestation, efficacy and treatment strategies in patients with severe warm autoimmune hemolytic anemia (w-AIHA).Methods:A total of 21 patients with w-AIHA who were hospitalized in Children′s Hospital of Capital Institute of Pediatrics from June 2007 to March 2019 were included, and the clinical characteristics, treatment strategies and responses were retrospectively analyzed.Results:A total of 21 children with severe w-AIHA had an average age of 8.0 (2.5, 20.0) months and a follow-up time of 33.0 (18.5, 110.0) months.In 10 (47.6%) cases, the hemoglobin levels were lower than 30 g/L.Evans′ syndrome was diagnosed in five(23.8%) cases.Five (23.8%) cases were secondary cases.Nine (42.8%) cases had a previous infection history and two cases were pollen-induced.Five (23.8%) cases had hemolytic crisis.A total of 12 (57.1%) cases had cross-matching difficulty.Eight (38.1%) cases were admitted to the ICU, and five (23.8%) cases had shock.All children received corticosteroids and intravenous immunoglobulin, 16 (76.2%) cases were treated with second-line regimens (cyclophosphamide and rituximab, etc.), 15 cases had complete response, three cases had partial response and three cases had no response and died.Conclusion:Infection is an important predisposing factor in children with severe w-AIHA, and secondary cases have a higher proportion, mainly caused by immunodeficiency disease.Patients tend to have a high incidence of hemolytic crisis and have difficulty in matching and transfusion.Therefore, transfusion is the key for successful rescue.It is suggested that children with severe w-AIHA require ICU admission for early monitoring and rituximab should be applied in advance to ensure successful transfusion.