In this prospective study, we measured the ST segments, heart rate-systolic BP product (RPP), respiratory rate to tidal volume ratio (RVR), and pulse oximetry saturations of patients in our medical/cardiac ICUs before and during weaning from mechanical ventilation. Ninety-three patients were enrolled with a mean age of 66.5 +/- 15.0 years (mean +/- SD), mean acute physiology and chronic health evaluation (APACHE) II score of 16.0 +/- 6.9, and mean duration of mechanical ventilation of 5.2 +/- 8.6 days. Forty-nine patients had coronary artery disease (CAD). Six of 93 patients (6.4%) experienced ECG evidence of ischemia during weaning. Five of these six had a precedent history of CAD and four failed initial weaning attempts (22% of patients with CAD who failed weaning). The RPP, for the group as a whole, increased significantly during weaning from 12.0 +/- 3.1 to 13.4 +/- 4.0 mm Hg.bpm.10(3) (p<0.01). The rate to volume ratio did not change significantly during weaning, except in the subgroup of patients who failed to wean, in whom it increased from 98.4 +/- 45.2 to 124.9 +/- 54.9 bpm/L (p<0.05). Oxygenation also decreased significantly from 0.98 +/- 0.02 to 0.96 +/- 0.03 and was significantly associated with weaning failure (risk ratio [RR]=3.9; 95% confidence interval [CI]=1.7 to 9.0). Thirty-seven patients failed the initial weaning attempt. Cardiac ischemia (RR= 1.8; 95% CI=1.0 to 3.4) and an increased RVR (RR=1.7; 95% CI=0.9 to 3.4) tended to increase the risk of weaning failure. Cardiac ischemia, although infrequent (6%) in the general population of weaning medical/cardiac ICU patients, should be considered in patients with CAD who fail to wean.