Background Elexacaftor/Tezacaftor/Ivacaftor (ETI) improved clinical outcomes in patients with cystic fibrosis having at least one copy of the Phe508del CFTR mutation [1]. However, ETI safety and efficacy in pediatric setting is poorly documented. Methods A retrospective, single-center study of 27 patients, aged 6-17 years, followed for at least 6 months between October 2022 and March 2024, was performed. The primary outcome was to evaluate the change of lung function (ppFEV1 and ppFVC) at 6 and 12 months after the initiation of ETI. Secondary outcomes included the number of pulmonary exacerbations, nutritional status (BMI, z-score-weight and z-score-height), sweat chloride concentration (SwCl), CFQ-R score and adverse events. Results After 12 months of treatment, ETI improved the ppFEV1 from basal mean of 88 to 103 (p=0,013) and ppFVC absolute change of 6% after six months with value stabilization at subsequent follow-up. BMI z-score-weight and z-score-height improved over the 12-month treatment period when compared to the pretreatment baseline. SwCl decreased rapidly through week 24, with a mean treatment difference of −44 mmol/L compared to mean baseline value (p<0.001). PEx rate decreased by 27,6 % after 12 months of treatment. CFQ-R score increased by 14 points from baseline (p<0,001). AEs occurred in 14.8% (n=4) of patients. All adverse events were reversible and mild to moderate in severity and they disappeared with dosage reduction. Conclusions ETI therapy improved lung function, nutritional status and quality of life in pediatric patients. ETI resulted in an acceptable adverse event and tolerability profile with no permanent treatment discontinuations.