Objective: To assess the association between adherence with fluticasone propionate/salmeterol combination (FSC) product in a single inhaler and asthma care utilization and costs in asthma patients in typical US clinical practice. Methods: Retrospective longitudinal analysis using linked medical and pharmacy claims from a managed care database representing >70 US health plans. Subjects included those with two prescriptions for FSC after January 1, 2000 (first prescription 'index date') and diagnosis of asthma. Follow-up was defined as time from index date to disenrollment or discontinuation of FSC (180 days without supply), receipt of different controller, or 24 months post-index. Patients were excluded if: 512 months continuous enrollment pre-index, 512 months of follow-up, diagnoses of COPD or respiratory cancer, use of ipratropium, or age 512 years. Effect of FSC adherence on asthma-related outcomes (short-acting beta-agonist use (SABA), corticosteroid use (CS), emergency department (ED) visit/hospitalizations) and asthma-related health plan costs during each quarter post-index and FSC adherence in prior quarter controlling for demographics, time since index, season, comorbidities, pre-index medications, utilization, and cost. Results: 12907 patients were identified: mean age, 40 years; mean follow-up, 20 months; mean quarterly FSC adherence, 54%; mean quarterly incidence of asthma-related ED visit/hospitalization, 1.12%. After adjusting for baseline characteristics, each 25% improvement in adherence was associated with a 10% reduction in the odds of asthma-related ED visit or hospitalization (p<0.001), a 10% reduction in the odds of receiving SABA (p<0.001), a 3% reduction in the odds of receiving a CS (p=0.027). However, total asthma-related costs also increased 23% for each 25% increase in the use of FSC. Conclusions: Despite the limitations of the study, this analysis shows that improving compliance with an asthma controller medication such as FSC may help reduce the burden of asthma.