Our goal was to evaluate the accuracy of a prediction equation that estimates the minimal level of pressure support (PS) required to overcome the resistance of the ventilator circuit and the endotracheal tube during mechanical ventilation. We calculated the minimal PS (PSmin) by means of the relationship between airway resistance and peak inspiratory flow rate during mechanical ventilation. Measurements of breathing pattern, flow rates, work of breathing (WOB), pressure time product (PTP), and PEEPi were made during several modes of ventilation (PSmin, PSmin + 25 percent, PSmin-25 percent, flow by, CPAP 0 cm H2O) and while breathing through an endotracheal tube (ETT) and spontaneous breathing (EXT). The WOB was significantly higher during EXT than PSmin, PSmin-25 percent, and ETT (1.04 vs 0.45, 0.54, and 0.74 J/L, respectively, p < 0.05). An unexpected finding was a higher WOB and PTP during EXT as compared with ETT in six of seven of our patients (1.04 vs 0.74 J/L). Examination of breathing pattern and flow volume loops in these two breathing modes raises the possibility that the post-EXT pathology increases in WOB is related to upper airway abnormality. Because of this, our predicted PSmin underestimated the WOB required for spontaneous breathing immediately post EXT.