This retrospective analysis of data from two multi-center, randomized, double-blind, parallel group studies compared the efficacy of fluticasone propionate/salmeterol (FSC) 250/50 mcg 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 FEV(1)AUC(0-6h) from baseline and the magnitude of improvement was larger in reversible patients. FSC increased FEV(1)AUC(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 < or = 0.041) in non-reversible patients. After 8 weeks, in both the reversible and non-reversible populations, the FEV(1) AUC(0-6h) significantly increased with FSC treatment (p < or = 0.002) and significantly decreased with IB/ALB (p < or = 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 < or = 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.