OBJECTIVES: To compare effectiveness of compliance on healthcare utilization between montelukast and standard therapy (inhaled corticosteroid - ICS) patients. Indicators for health care resource use include drug use, ER visits, and total charges. METHODS: Retrospective cohort analysis using LifeLink employer claims database of 1.6 million Americans. ANOVA models examined healthcare resource use of montelukast and ICS patients in six months prior (pre-period) and six month following (post-period) new treatment of interest adjusting for age, gender, region, plan type, and prescriber specialty. RESULTS: The study cohort consisted of 3,775 montelukast patients and 7,331 ICS patients. Average compliance, defined as medication possession ratio, of montelukast patients (63%) was significantly greater (p=0.001) than that of ICS patients (31%). Montelukast patients were more likely to receive short-acting beta-agonist therapy in pre-period than ICS patients (p=0.001), which suggests more severe patients in montelukast group, but there was no significant difference between two groups in post-period (p=0.854). Among patients with concomitant methylxanthine therapy, montelukast patients had more days of methylxanthine therapy than ICS in pre-period (p<0.001), but there was no significant difference in post-period (p=0.130). For patients with at least one asthma-related ER visit, montelukast patients had more ER visits per patient than ICS patients in pre-period (p=0.010), but no significant difference was noted in post-period (p=0.325). Average total charges for montelukast were higher than for ICS patients in both pre-period (p<0.001) and post-period (p<0.001). CONCLUSIONS: Compliance with montelukast treatment was markedly better than with ICS therapy. Initially, montelukast patients were higher resource users than ICS patients. During six months treatment with montelukast, some healthcare resources used decreased to the level of ICS patients. Results suggest that markedly improved compliance of montelukast decreased asthma-related healthcare utilization, however total charges for montelukast patients remained higher than for ICS patients.