Objective: To compare, in elderly Medicare beneficiaries, chronic obstructive pulmonary disease (COPD)-related healthcare costs for patients initiating treatment with fluticasone propionate/salmeterol 250 μg/50 μg (FSC) with those for patients initiating treatment with ipratropium bromide/albuterol (IPA), ipratropium bromide (IPR), and tiotropium bromide (TIO).Methods: In this retrospective, observational, cohort study, COPD-related medical costs (inpatient/emergency department, outpatient) and pharmacy costs were assessed in Medicare beneficiaries ≥65 years old who were enrolled in a commercial Medicare health maintenance organization plan and had a diagnosis of COPD (ICD-9-CM codes 491.xx, 492.xx, or 496.xx) within 12 months before initial treatment with FSC, IPA, IPR, or TIO.Results: In these ≥65-year-old patients (N=14,689), initial maintenance treatment with FSC was associated with total COPD-related cost savings (medical + pharmacy) of $295 versus IPA, $1,235 versus IPR, and $110 versus TIO (p<0.05, each comparison) over a 1-year follow-up period.Conclusions: Initiation of maintenance therapy with FSC was associated with significant reduction in total costs (medical + pharmacy) relative to costs associated with the short-acting anticholinergic bronchodilators IPR and IPA and the long-acting anticholinergic bronchodilator TIO in an elderly Medicare-eligible population. These data considered in the context of the substantial efficacy and effectiveness data suggest that early introduction of maintenance treatment with FSC has both clinical and economic benefits. Limitations inherent in handling of administrative data include lack of objective clinical measures such as spirometry and smoking status. Furthermore, accuracy of diagnosis codes cannot be verified.