OBJECTIVES: The combination drug, fluticasone propionate and salmeterol (FPS), and zafirlukast, a leukotriene receptor antagonist (LTRA), represent two classes of asthma controller medications. FPS has been shown to be more clinically effective compared to drugs in the LTRA group. Our objective is to determine the financial benefits associated with managing severe adult asthma with FPS or zafirlukast, from a self-insured employer's perspective. METHODS: We developed a Markov model to predict the health outcomes and costs for asthma in a hypothetical, commercially insured population. The model predicts asthma costs of hospitalizations, pharmacy, professional visits, and outpatient services. It also estimates non-medical costs using lost workdays due to asthma. We used $2.40 as the plan's net cost per patient per day for FPS and $1.48 for zafirlukast. The beneficial effects of each drug are modeled by a reduction in health service utilization and lost workdays. The model assumes that all severe adult asthma patients not well managed at baseline are optimally managed in the intervention scenario, with 100% medication compliance. The cost-benefit is expressed as net savings in medical and non-medical costs. RESULTS: For a commercially insured population of 100,000 members, the model predicted 276 severe adult asthma cases, and net savings of $0.13 per member per month (PMPM) over 3 years for FPS. Zafirlukast is estimated to take more than three years to break even. For both drugs, about 46% of total savings are from non-medical savings. A sensitivity analysis shows that FPS continues to be cost beneficial over 3 years as long as the medication compliance is 63% or more. CONCLUSIONS: Managing adult severe asthma with FPS is predicted to be cost-beneficial in the short term from a self-insured employer's perspective.