Background: Asthma control is the goal of therapeutic interventions. In observational studies, the use of short-acting beta-agonises (SABAs) is a surrogate for symptoms and emergency department or hospital events for exacerbations. Objective: To compare asthma exacerbations, medication switch, and use of SABAS among 3 treatment cohorts: fluticasone propionate and salmeterol as a single inhaler (FSC), fluticasone and salmeterol as separate inhalers (FP + SAL), and fluticasone propionate alone (FP). Methods: Administrative claims data from approximately 10 million individuals from April 2000 to December 2002 were examined. Patients 15 years or older with claims for asthma, SABAs, and study medications were included in the study. Asthma-related medical and pharmacy claims were evaluated. Multivariate regression techniques were used to model the outcomes of interest, controlling for patient characteristics. Results: The odds of a hospitalization or emergency department event were significantly lower for the patients receiving FSC (n = 1,013) compared with those receiving FP (n = 1,130) (odds ratio, 0.75; 95% confidence interval, 0.61-0.93) and those receiving FP + SAL (n = 271) (odds ratio, 0.69; 95% confidence interval, 0.51-0.95). Patients receiving FSC also had a significantly lower risk of switch or discontinuation of index medication and lower rates of postindex SABA use. Conclusion: In this analysis, patients receiving FSC had lower rates of asthma-related symptoms and exacerbations as measured by SABA refills and hospitalization, respectively, when compared with patients receiving either FP or FP + SAL. This observational examination of medical and pharmacy claims data adds to the clinical reports that demonstrate the increased effectiveness of FSC when compared with FP or FP + SAL.