Hypothesis: Using increase in the lung clearance index (LCI) as a trigger for bronchoalveolar lavage (BAL) and associated antimicrobial treatment might benefit clinical outcomes in children with cystic fibrosis (CF). Methods: A 2-year, longitudinal, interventional, randomized, controlled pilot study with quarterly visits in 5–18 years old children with CF. LCI and z-scores for the forced expired volume in 1 s (zFEV₁) and body mass index (zBMI) were obtained at every visit, CF Questionnaire-revised (CFQ-R) yearly and BAL and chest computed tomography at first and last visit. Children in the intervention group had BAL performed if LCI increased >1 unit from a fixed baseline value established at first visit. If the presence of a pathogen was documented in the BAL fluid, treatment was initiated/altered accordingly. Results: Twenty-nine children with CF were randomized to the control (n = 14) and intervention group (n = 15). The median (interquartile range) number of BAL procedures per child was 2.5 (2.0; 3.0) and 6.0 (4.0; 7.0) in the control and intervention group, respectively. There was no significant difference between groups in slope for the primary outcome LCI; difference was 0.21 (95% confidence interval: -0.45; 0.88) units/year. Likewise, there was no significant difference between groups in slope for the secondary outcomes zFEV₁, zBMI, CFQ-R respiratory symptom score and the proportion of total disease and trapped air on chest computed tomography. Conclusions: LCI-triggered BAL and associated antimicrobial treatment did not benefit clinical outcomes in a small cohort of closely monitored school-age children with CF.