During the course of a critical illness, many patients become ventilator dependent. The standard assessment criteria are not always accurate in predicting potential for extubation. This investigation was designed to analyze whether the work of breathing (WOB) was a more reliable predictor of ventilator dependence. Twenty consecutive ventilator-dependent patients were prospectively studied. Nineteen required ventilator support for greater than 2 wk and all were considered ventilator dependent because of their inability to tolerate weaning trials. The oxygen consumption (VO2) and resting energy expenditure were measured using a metabolic gas monitor. Respiratory mechanics and arterial blood gas measurements were obtained, and the deadspace to tidal volume ratio (VD/VT) was calculated. The WOB was determined by the difference in VO2 between spontaneous and mechanical ventilation, and expressed as a percentage of VO2 during mechanical ventilation. Five of eight patients with a WOB less than 15% (mean 1.9) were extubated within 2 wk of study, while none of 12 patients with a WOB greater than or equal to 15% (mean 34) were able to be extubated in this period. The differences in the WOB between the two groups were statistically significant (p less than .01), while there was no significant difference in mechanics, PaCO2, VD/VT or measured resting energy expenditure. These data support the use of WOB determinations in evaluating extubation potential. Using a reference value for the WOB of 15%, this study had a sensitivity of 100% and a specificity of 80%. This proved to be of greater predictive value than traditional criteria.