This multicenter study evaluated the efficacy of adding salmeterol or montelukast to patients whose conditions were suboptimally controlled by ICS therapy. Four hundred forty-seven patients were randomized to receive 12 weeks of therapy with fluticasone, 100 μg, plus either salmeterol, 50 μg twice daily, or oral montelukast, 10 mg daily, in a double-blind, double-dummy protocol. The combination of a therapy with a long-acting β-agonist and ICSs resulted in significantly greater morning peak expiratory flow (24.9 vs 13.0 L/min, respectively; p < 0.001), FEV1 at clinic visits (0.34 vs 0.20 L, respectively; p < 0.001), and the percentage of days with no albuterol use (26.3% vs 19.1%, respectively; p = 0.032). Asthma exacerbation rates were also significantly lower in the salmeterol/fluticasone group (p = 0.031). Of note, patients in the salmeterol/fluticasone group still used > 2 puffs per day albuterol after 12 weeks of treatment.