With increasing pressure support ventilation (PSV), a form of pneumatically triggered ventilation, there can be an increase in wasted inspiratory efforts (neural inspiratory efforts that fail to trigger the ventilator). With neurally adjusted ventilatory assist (NAVA), a mode of ventilation controlled by the electrical activity of the diaphragm (EAdi), synchrony should be maintained at high levels of assist. The aim of this study was to evaluate the response to increasing levels of PSV and NAVA on synchrony and diaphragm unloading in lung-injured rabbits. Animals were ventilated on PSV or NAVA in random order, each at three levels. We measured neural and ventilator respiratory rates, EAdi, transdiaphragmatic pressure (Pdi), and tidal volume (VT). At low PSV, 95% of neural efforts were triggered, compared with high PSV, where only 66% of the neural efforts were triggered. During NAVA, all neural efforts were triggered, regardless of level. Increasing NAVA levels reduced EAdi and Pdi-time products by 48% (p < 0.05) and 66% (p < 0.05). In contrast, increasing PSV did not reduce the diaphragm electrical activity-time product and increased the transdiaphragmatic pressure-time product (p < 0.05) due to the increased wasted efforts. We conclude that synchrony with the ventilator is an important determinant for diaphragm unloading.