A new class of asthma drugs modifying the leukotriene pathway was introduced in 1996. The authors investigated outcome changes associated with use of the leukotriene-receptor antagonist zafirlukast. The study group included patients with asthma (12-64 yr), most with mild-to-moderate, persistent asthma, who had at least two zafirlukast prescriptions within 90 days after the start of zafirlukast treatment. Zafirlukast treatment was associated with reductions in occurrence of outpatient visits, emergency department visits, inpatient stays, and prescriptions for short-acting beta-adrenergic agonists in the next six months (all P < .05). A 12-month pre- and post-zafirlukast treatment comparison in a smaller group of patients and a classification of patients into three mutually exclusive outcome groups (increase, decrease, or no change in outcome events) verified the majority of the findings. A cost analysis from a third-party perspective indicated that costs of zafirlukast treatment were more than offset by cost savings associated with the reductions in outcome events.