Objective: To observe the application value of plasma exchange and leuko-reduced erythrocyte suspension transfusion in autoimmune hemolytic anemia (AIHA) with warm-reactive antibodies. Methods: A total of 158 patients with AIHA with warm-reactive antibodies in our hospital were selected. Among them, there were 100 cases treated with plasma exchange and leuko-reduced erythrocyte suspension transfusion (the observation group), and 58 cases treated with blood transfusion only (the control group). Levels of related complements (C3, C4), anti-double-stranded DNA (ds-DNA) titer, hemoglobin (Hb), reticulocyte (Ret), red blood cell count (RBC) and serum total bilirubin (TBIL) before and after treatment, and adverse reactions were compared between the 2 groups. Results: After treatment, the levels of C3, C4, anti-ds-DNA, and Ret in the observation group were significantly lower than those in the control group (P<0.05), while the levels of Hb and RBC were significantly higher than those in the control group (P<0.05). Serum Hb was significantly positively correlated with RBC (P<0.05), and significantly negatively correlated with Ret in AIHA patients (P<0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P>0.05). Conclusion: Plasma exchange and leuko-reduced erythrocyte suspension transfusion can effectively remove pathogenic antibodies and complements, increase their serum Hb and RBC levels and reduce Ret levels in patients with AIHA with warm-reactive antibodies, with safety. And it is of important application value.