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Background: COPD guidelines report that systemic corticosteroids are preferred over inhaled corticosteroids in the treatment of exacerbations, but the inhaled route is considered to be an option., Objectives: To conduct a systematic review and meta-analysis regarding the efficacy and safety of inhaled corticosteroids for COPD exacerbations. The second objective was to provide pharmacologic and clinical perspectives of inhaled corticosteroids for COPD exacerbations., Methods: The primary outcome was a change in FEV 1 baseline versus the last measured value. Secondary outcomes were a change in (P aO 2 ) and (P aCO 2 ) baselines versus the last measured values; FEV 1 , P aO 2 , and P aCO 2 at 24 or 72 h; and hyperglycemia., Results: Each of the 9 studies included in the meta-analysis was conducted in subjects who were hospitalized and not critically ill. Our meta-analysis indicated that high-dose nebulized budesonide 4-8 mg/d was noninferior to systemic corticosteroids on the change in FEV 1 between baseline and the last measured value (mean difference of 0.05, 95% CI -0.01 to 0.12, P = .13) and P aCO 2 (mean difference of -1.14, 95% CI -2.56 to 0.27, P = .11) but of inferior efficacy for P aO 2 changes (mean difference of -1.46, 95% -2.75 to -0.16, P = .03). Hyperglycemia was less frequent with high-dose nebulized budesonide (risk ratio, 0.13; 95% CI 0.03-0.46; P = .002)., Conclusions: Based on our meta-analysis with a change in FEV 1 as the primary end point, high-dose nebulized budesonide was an acceptable alternative to systemic corticosteroids in hospitalized subjects with COPD exacerbations who were not critically ill. Additional well-designed prospective studies are needed in both the acute care and ambulatory settings. We provide perspective on how this evidence might be applied in clinical practice., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2018 by Daedalus Enterprises.)