Objective: Investigate the cardiorespiratory effects of non-invasive neurally adjusted ventilatory assist (NIV-NAVA), non-synchronized nasal intermittent positive pressure ventilation (NIPPV), and nasal continuous positive airway pressure (NCPAP) during the critical period shortly after extubation. Hypothesis: Levels of non-invasive pressure support provided and/or presence of synchronization can affect cardiorespiratory parameters. Study design: Randomized crossover trial. Patient-subject selection: Infants with birth weight (BW) ≤ 1250g undergoing their first planned extubation were randomly assigned to all 3 modes following extubation. Methodology: Electrocardiogram and electrical activity of the diaphragm (Edi) were recorded during 30min on each mode. Analysis of heart rate variability (HRV), diaphragmatic activity (Edi area, breath area, amplitude, inspiratory and expiratory times) and respiratory variability (RV) were compared between modes. Results: 23 enrolled infants had full data recordings and analysis: median [IQR] gestational age = 25.9 weeks [25.2-26.4], BW = 760g [595-900], and post-natal age 7 [4-19] days. There were no differences in HRV parameters between modes. During NIV-NAVA and NIPPV, diaphragmatic activity was significantly lower and RV higher than NCPAP. Delivered peak inflation pressures (PIPs) were lower during NIV-NAVA than NIPPV (14 cmH2O [13-16] vs cmH2O 16 [16-17]; p<0.001). However, due to a significantly higher proportion of assisted breaths (99% [92-103] vs. 51% [38-82]; p<0.001) NIV-NAVA provided a higher mean airway pressure (MAP)(9.4 cmH2O [8.2-10.0] vs. 8.2 cmH2O [7.6-9.3]; p=0.002). Conclusions: NIV-NAVA and NIPPV applied shortly after extubation were associated with positive cardiorespiratory effects. This effect was more evident during NIV-NAVA where patient-ventilator synchronization provided a higher MAP with lower PIPs.