This retrospective analysis of data from two multi-center, randomized, double-blind, parallel group studies compared the efficacy of fluticasone propionate/salmeterol (FSC) 250/50mcg twice daily with ipratropium bromide/albuterol (IB/ALB) 36/206 mcg four times daily in albuterol-reversible (n=320 [44%]) and non-reversible (n=399 [56%]) patients with COPD. In reversible and non-reversible patients, both treatments significantly increased FEV₁AUC_0–6h from baseline and the magnitude of improvement was larger in reversible patients. FSC increased FEV₁AUC_0–6h by 1.46±0.08 and 1.98±0.13 l-h at Day 1 and Week 8, respectively, in reversible patients, compared with 0.71±0.06 and 0.94±0.10 l-h in non-reversible patients (p<0.001). With IB/ALB, increases were 1.46±0.08 and 1.19±0.11 l-h at Day 1 in reversible patients and Week 8, respectively, and 0.89±0.06 and 0.74±0.09 l-h (p≤0.041) in non-reversible patients. After 8 weeks, in both the reversible and non-reversible populations, the FEV₁ AUC_0–6h significantly increased with FSC treatment (p≤0.002) and significantly decreased with IB/ALB (p≤0.010). In both reversibility groups, improvement in Transition Dyspnea Index (TDI) scores, overall daytime diary symptom scores and nocturnal symptom measures were significantly greater with FSC treatment compared with IB/ALB (p≤0.044). Reversibility status was not predictive of the magnitude of reduction in symptom scores. We conclude that both reversible and non-reversible patients receive greater clinical benefit with FSC compared with IB/ALB and acute bronchodilator reversibility is not useful for differentiating patients based on symptomatic responses to FSC compared with IB/ALB.