To compare the cost-effectiveness of 2 commonly used asthma controllers, fluticasone and montelukast, in a population of pediatric patients with mild-to-moderate persistent asthma.A total of 154 patients (aged 6–14 years) who participated in the Pediatric Asthma Controller Trial (PACT) were included in the study.This study extracted data from the PACT study, a randomized controlled, double-blind, multicenter trial that studied treatment regimens in children with mild-to-moderate persistent asthma. Both effectiveness and cost measures were used to determine a cost-effectiveness analysis of the 2 controller medications: fluticasone (100 μg twice daily) and montelukast (5 mg daily), given for 48 weeks. Effectiveness measures included (1) asthma-control days (ACDs), (2) improvement in forced expiratory volume in 1 second (FEV1), and (3) the number of exacerbations avoided. Cost measures were taken from (1) direct costs from a third-party payer's perspective, including the sum of costs from asthma-related medication, emergency department visits, and regular physician's office visits, and (2) societal costs, which were the direct costs plus productivity losses from asthma-related missed school or work. Cost-effectiveness analysis was then used to compare the effectiveness of the different treatments relative to their costs. Cost-effectiveness analysis was also performed for subgroups on the basis of the phenotypic factors of exhaled nitric oxide (eNO) and the provocative concentration that causes a 20% decrease (PC20) in the forced expiratory volume in 1 second (FEV1).Of the 154 patients analyzed, 79 received fluticasone and 75 received montelukast. There were no statistical differences in demographics among the participants. When effectiveness measures were compared, fluticasone showed significantly higher effectiveness with respect to ACDs, improvement in FEV1, and the number of asthma exacerbations (P < .01). Direct costs during the study period were $759 for fluticasone and $1189 for montelukast (P < .001). Societal costs were $1075 for fluticasone and $1673 for montelukast (P < .001). Thus, fluticasone was shown to be more cost-effective. In the subgroup analysis, fluticasone was more cost-effective compared with montelukast for the subgroups with high eNO levels (eNO ≥ 25 ppb) and more-responsive PC20 (PC20 < 2 mg/mL).In children with mild-to-moderate persistent asthma, fluticasone had lower cost and higher effectiveness when compared with montelukast, especially in patients with more airway inflammation and more responsivity to methacholine.Few evaluations exist for the cost-effectiveness of asthma controller regimens for children. The results of the study were consistent with the National Asthma Education and Prevention Program guidelines, which recommend inhaled corticosteroid monotherapy as the preferred asthma controller option for mild-to-moderate persistent asthma in children.