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Background: Noninvasive ventilation (NIV) is increasingly utilized in infants and young children, though associated with high failure rates due to agitation and poor compliance, mostly if patient-ventilator synchronization is required., Methods: A retrospective cohort study was carried out in an academic pediatric intensive care unit (PICU). Dexmedetomidine (DEX) was infused as unique sedative in 40 consecutive pediatric patients (median age 16 months) previously showing intolerance and agitation during NIV application., Results: During NIV clinical application both COMFORT-B Score and Richmond Agitation-Sedation Scale (RASS) were serially evaluated. Four patients experiencing NIV failure, all due to pulmonary condition worsening, required intubation and invasive ventilation. 36 patients were successfully weaned from NIV under DEX sedation and discharged from PICU. All patients survived until home discharge., Conclusion: Our data suggest that DEX may represent an effective sedative agent in infants and children showing agitation during NIV. Early use of DEX in infants/children receiving NIV for acute respiratory failure (ARF) should be considered safe and capable of improving NIV, thus permitting both lung recruitment and patient-ventilator synchronization.