An imbalance between work of breathing and respiratory muscle capacity often results in rapid, shallow breathing (increased respiratory rate/tidal volume [f/VT]). Because this imbalance commonly causes unsuccessful weaning from mechanical ventilation, it is not surprising that an elevated f/VT accurately predicts weaning failure. However, while studying extubation outcome, we observed that women and patients with narrow endotracheal tubes are often successfully extubated with an elevated f/VT. We studied 218 medical patients in the intensive care unit who had a f/VT measured through an oral endotracheal tube (off of ventilatory support) during 1 min of spontaneous respiration at the onset of a weaning trial that culminated in extubation. Men and women were comparable at the onset of mechanical ventilation and weaning trials in severity of illness, etiology of respiratory failure, ventilator settings, and gas exchange data. Women were found to have a higher f/VT (79 +/- 5 versus 56 +/- 3 breaths/L, p < 0.001), lower tidal volumes (381 +/- 14 versus 494 +/- 13 ml, p < 0.001), and higher respiratory rate 26 +/- 1 versus 24 +/- 1, p < 0.05). The differences persisted after controlling for extubation outcome. Smaller endotracheal tubes were associated with a higher f/VT, especially for women (< or = 7 mm, 86 +/- 6 versus > 7 mm, 68 +/- 6, p < 0.05). Women were more likely to have a f/VT > or = 100 (19/82 [women] versus 10/136 [men], p < 0.001). Although the overall incidence of extubation failure was similar (11/82 [women] versus 23/136 [men], p = NS), among patients with f/VT > or = 100, men were more likely to require reintubation (3/19 [women] versus 5/10 [men], p = 0.08). We conclude that women, especially when breathing through small endotracheal tubes, have a higher f/VT (including likelihood of f/VT > or = 100) than men, independent of extubation outcome. Consideration of factors that elevate the f/VT, unrelated to physiologic work of breathing and respiratory muscle capacity, should improve application of this index to extubation decision making.