OBJECTIVES: To compare medical costs and utilization in patients on single controller inhaled corticosteroid (ICS) to other asthma drug regimens. Medical costs and health care utilization associated with asthma and the variation by treatment are poorly understood. METHODS: Direct medical costs and utilization were captured from administrative electronic databases from continuously-enrolled health plan members with asthma aged 5 years or older with comprehensive medical and drug coverage. Asthma patients were identified during 2002, categorized into 14 asthma drug treatment groups based on 2003 prescription records, and had total medical costs and utilization determined in 2004, adjusting for demographics, insurance types, asthma risk, co-morbidity, and treatment selection propensity scores. RESULTS: In total, 96,631 patients met the study eligibility criteria. Patients averaged 37.5+23.1 years of age and were 57% female, 14% Medicare, 4% Medicaid, and had a median family income of $64,967+29,285. Total unadjusted direct medical costs/patient/year averaged $3745 ($3298 low asthma risk versus $6797 high asthma risk, p <.0001). Adjusted total and asthma-related costs were significantly lower with single controller ICS compared to single controller leukotriene modifiers (p CONCLUSION: Both costs and asthma-related utilizations are significantly less in the year after being dispensed single controller ICS compared to single controller leukotriene modifiers or combination controllers. These findings from a typical practice setting provide economic support for international guidelines that recommend single controller ICS as the preferred initial asthma controller treatment.