Introduction: Acute lower respiratory infection (ALRI) of viral etiology is a frequent consultation in pediatrics. Post-infectious bronchiolitis obliterans (PIBO) is a rare and potentially severe disorder following ALRI, characterized by partial or complete obstruction of the small airways by inflammatory tissue. There is evidence that macrolides reduce morbidity and mortality in diffuse panbronchiolitis, which may have similar inflammatory and obstructive components. We hypothesized that the effect of azithromycin (AZ) may improve lung function and reduce pulmonary exacerbations in PIBO. Methods Study design: A double-blind, randomized, placebo-controlled trial. Patients: We enrolled patients with PIBO followed-up at the Pulmonology department between 5 years to 18 years. Treatment regimen: The patients were randomized to receive active drug or placebo three times a week. Clinical evaluation: Clinical evaluation, pulse oximetry, lung function, and 6-min walk test were performed before and after study initiation and at 1, 3, and 6 months. CT scan and a quality of life questionnaire were performed at the beginning and the end of the Study. Results: 29 patients, 15 in G1 (10 males) and 14 in G2 (7 males) were included. There were no significant differences in FVC, FEV1, TLC, RV, or sGaw between the treatment group and controls. In addition, no significant differences were observed in exacerbations, quality of life questionnaire, or HRCT scan scores. Conclusion: No differences were observed between the groups. Further studies are necessary to allow us to find a better treatment, as azithromycin does not seem to be efficacious.