Corticosteroids are often used in the outpatient treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD). To date, there are few data documenting the benefit of this practice. The objective of this randomized, double-blind, placebo-controlled trial was to assess the efficacy of corticosteroids in the outpatient treatment of COPD exacerbations. Twenty-seven patients presenting with acute COPD exacerbation were studied. In addition to continuing their previous medications and increasing their use of beta-agonists, patients were randomized to receive a 9-d tapering dose of either oral prednisone or placebo. Treatment with prednisone rather than placebo resulted in a more rapid improvement in arterial PO2 (PaO2) (1.12 mm Hg/d versus -0.03 mm Hg/day; p = 0.002), alveolar-arterial oxygen gradient (A-aDO2) (-1.16 mm Hg/d versus -0.03 mm Hg/day; p = 0.04), FEV1 (0.05 L/d versus 0.00 L/d; p = 0.006), and peak expiratory flow (PEF) (0.15 L/s/d versus 0.04 L/s/d; p = 0.009). Prednisone also resulted in fewer treatment failures (p = 0.002) and in a trend toward more rapid improvement in dyspnea scale scores. Outpatient treatment of acute COPD exacerbation with prednisone accelerates recovery of PaO2, A-aDO2, FEV1, and PEF, reduces the treatment failure rate, and improves subjective dyspnea.