Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and is the leading respiratory cause of childhood morbidity. BPD results in a significant burden to families and increased health care utilization. In the United States alone BPD accounts for over $2.4 billion in healthcare costs annually. Ventilator induced lung injury (VILI) an accepted and important contributor to BPD. Exposure to oxygen and positive pressure ventilation leads to developmental arrest and parenchymal injury in the immature preterm lung. Because even brief exposure to positive pressure ventilation is injurious, avoiding invasive intubated mechanical ventilation is the most widely acknowledged strategy to prevent VILI and the long-term sequela of BPD. Therefore, time on ventilators and rates of successful extubation are important endpoints of therapy. Lung protective strategies prioritize non-invasive respiratory support for preterm infants with respiratory failure, but failure rates of continuous positive airway pressure (CPAP) therapy are high. In meta-analysis of available trials, both synchronized and non-synchronized non-invasive positive pressure ventilation (NIPPV) are superior to CPAP for preventing extubation failure in preterm infants. A stronger effect size was observed for synchronized NIPPV vs. CPAP than for non-synchronized NIPPV vs. CPAP. However, until recently no FDA-approved reliable methods to provide synchronized NIPPV for preterm infants were available in the US Neurally Adjusted Ventilatory Assist (NAVA), an FDA approved technology, is a novel method to synchronize ventilatory support with infant respiratory drive. This effective non-invasive synchronization matches electrical diaphragmatic activity to deliver synchronized and accurate tidal volumes in proportion to the neural signal. To date, the clinical impact of non-invasive NAVA (NIV-NAVA) on clinical outcomes in preterm infants has not been established. In these clustered UG3/UH3 and U24 applications, we propose a pragmatic, unblinded, phase III clinical trial in 478 extremely preterm infants of 24 0/7- 27 6/7 weeks gestational age to determine if NIV-NAVA, compared with non-synchronized NIPPV, prevents extubation failure within 5 days of extubation from mechanical ventilation.