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Introduction: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) requiring admission to the intensive care unit (ICU) result in high mortality and healthcare expenses. Systemic corticosteroids (CS) are a primary therapy for AECOPD patients admitted to the ICU. These patients are frequently treated with CS doses that are 5-10 times higher than recommended for non-ICU patients. The purpose of this study was to evaluate the efficacy and safety of high-dose versus lower-dose CS in ICU patients with AECOPD. Hypothesis: Lower-dose CS therapy is as effective as high-dose therapy in ICU patients with AECOPD, but high-dose CS therapy results in more significant adverse effects. Methods: The Premier Perspective Database (January 1, 2003 to December 31, 2008) was utilized to study patients admitted to the ICU with a principal diagnosis of respiratory failure plus a secondary diagnosis of AECOPD, COPD, or emphysema (or reverse diagnostic order), and treated with CS within the first 48h. Patients were divided into high-dose (methylprednisolone or equivalent > 240 mg/day) or lower-dose (methylprednisolone or equivalent? 240 mg/day) groups based on CS dosage in the first 48h. The primary outcome was hospital length of stay (LOS). Results: 53,955 patients were enrolled: 32,230 in the high-dose CS group and 21,725 in the lower-dose group. Overall, 77% of patients were? 60 years old, 55% mechanically ventilated, 37% on noninvasive ventilation and 92% were prescribed antibiotics. Then mean ± SD total CS dose in the first 48h was 788 ± 828 mg in the high-dose group and 173 ± 100 mg in the lower-dose group. There were no differences in hospital LOS, ICU LOS or duration of mechanical ventilation between the lower-dose and the high-dose CS groups (p=NS). Insulin therapy (56% vs. 55%, p=0.03) and hyperglycemia (2.7% vs. 1.6%, p<0.0001) were increased in the high-dose versus the lower-dose group. Conclusions: Despite its use in the majority of patients, methylprednisolone dosages > 240 mg/day do not appear to improve clinical efficacy in ICU patients admitted with an AECOPD and may increase side effects. Prospective clinical trials are needed to identify the optimal CS dose in critically ill patients with AECOPD.