Rationale A pilot study (Bisgaard et al. AJRCCM 2003;167:379) had reported the efficacy of montelukast in post-RSV-bronchiolitic respiratory symptoms. Objectives To evaluate efficacy and safety of montelukast 4 and 8 mg in treating recurrent respiratory symptoms of post-RSV-bronchiolitis in children in a large, multicenter study. Methods This was a double-blind study of 3-24-month-old children who had been hospitalized for a first or second episode of physician-diagnosed RSV-bronchiolitis and testing positive for RSV. Patients (n=979) were randomized to placebo, montelukast 4 or 8 mg/day for 4 weeks (Period-I) and 20 weeks (Period-II). The primary endpoint was percentage symptom-free days (%SFD; day with no daytime cough, wheeze and shortness of breath, and no nighttime cough). Results No significant differences were seen between montelukast and placebo in %SFD over Period-I: mean±SD for placebo, montelukast 4 and 8 mg were 37.0±30.7, 38.6±30.4, and 38.5±29.9, respectively. Least-squares mean differences [95% CI] between montelukast 4 mg and placebo and between montelukast 8 mg and placebo were 1.9% [-2.9, 6.7] and 1.6% [-3.2, 6.5]. Secondary endpoints were similar across treatments. Both doses were generally well tolerated. During the first two treatment weeks, average %SFD was ~29%. In post-hoc analyses of patients (n=523) with persistent symptoms (%SFD 30% over Weeks 1-2), differences in %SFD were seen between montelukast and placebo over Weeks 3-24: difference were 5.7 [0.0, 11.3] for montelukast 4 mg minus placebo and 5.9 [0.1, 11.7] for montelukast 8 mg minus placebo. Conclusion In this study, montelukast did not improve respiratory symptoms of post-RSV-bronchiolitis in children. Clinical trials registration information available at www. clinicaltrials.gov, identifier code: NCT00076973