Background: Experimental clinical studies have demonstrated that the addition of salmeterol to inhaled corticosteroids (ICSs) is superior to the addition of montelukast to ICSs. Observational research from real-world clinical practice is needed to confirm these results. Objective: The present study was designed to assess, in clinical practice, the comparative impact on health care utilization and cost of 2 dual-controller therapies, ICS + salmeterol and ICS + montelukast. Methods: This study involved the use of a 24-month pre/post retrospective design in patients continuously enrolled in any of 14 United HealthCare plans. Outcomes assessed were post-index pharmacy costs, rates of emergency department visits and hospitalizations, numbers of filled prescriptions for short-acting β-agonists (SABAs), total asthma costs, and total health care costs. Results: Subjects in the ICS + salmeterol group had 35% fewer post-index SABA claims than subjects in the montelukast add-on group (P ≤ .05). Subjects using ICS + montelukast were 2.5 times more likely to have an asthma-related hospitalization than subjects using ICS + salmeterol (P ≤ .065). Total adjusted asthma costs were 63% higher for the patients receiving ICS + montelukast than for the patients receiving ICS + salmeterol (P ≤ .0001). In addition, total health care costs were 25% lower in the ICS + salmeterol group. (P ≤ .0004). Additional reductions in hospitalization and emergency department visits were observed when the patients on FP + salmeterol were studied separately. Conclusion: In comparison with the use of montelukast and ICS, the use of salmeterol and ICS was associated with a significant reduction in SABA use, decreased hospital event rates, and significantly lower total asthma care costs. (J Allergy Clin Immunol 2002;109:433-9.)