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First obinutuzumab application is associated with infusion related reactions (IRRs) that may discourage further continuation of the drug. During our clinical practice we have observed that chronic lymphocytic leukemia (CLL) patients with autoimmune hemolytic anemia (AIHA) prolongedly receiving corticosteroids do not develop obinutuzumab IRRs. Therefore, we decided to apply prolonged corticosteroid premedication with methylprednisolone in dose 1-1.5 mg/kg for ≥7 days to all further obinutuzumab candidates. Here we present non-randomized comparison of 28 consecutive previously untreated CLL patients receiving prolonged corticosteroid premedication (15 patients) or standard premedication (13 patients) prior to the first obinutuzumab infusion. Prolonged corticosteroid premedication resulted in significant reduction of all-grade (20% vs 61.5%; p = .025) and grade III (0% vs 23.1%; p = .049) obinutuzumab IRRs. Prolonged corticosteroid premedication did not significantly affect occurrence of infective complications. Patients with CLL and AIHA receiving obinutuzumab showed continuous and stable increase in hemoglobin levels concomitantly with decrease in parameters of hemolysis.