This study compared four methods of weaning patients from mechanical ventilation: intermittent mandatory ventilation, pressure-support ventilation, intermittent trials of spontaneous breathing, and a once-daily trial of spontaneous breathing. The study involved 546 patients who had received mechanical ventilation for an average of 7.5 ± 6.1 days. Patients who had respiratory distress during a two-hour trial of spontaneous breathing were randomly assigned to one of the four weaning techniques. The median duration of weaning was 5 days for intermittent mandatory ventilation, 4 days for pressure-support ventilation, 3 days for intermittent trials of spontaneous breathing, and 3 days for a once-daily trial of spontaneous breathing. After adjusting for covariates, the rate of successful weaning was significantly higher with a once-daily trial of spontaneous breathing compared to intermittent mandatory ventilation (rate ratio, 2.83; P<0.006) and pressure-support ventilation (rate ratio, 2.05; P<0.04). There was no significant difference in the rate of success between once-daily trials and multiple daily trials of spontaneous breathing. The study concluded that a once-daily trial of spontaneous breathing led to extubation about three times faster than intermittent mandatory ventilation and twice as fast as pressure-support ventilation. Multiple daily trials of spontaneous breathing were equally successful.This study compared four methods of weaning patients from mechanical ventilation: intermittent mandatory ventilation, pressure-support ventilation, intermittent trials of spontaneous breathing, and a once-daily trial of spontaneous breathing. The study involved 546 patients who had received mechanical ventilation for an average of 7.5 ± 6.1 days. Patients who had respiratory distress during a two-hour trial of spontaneous breathing were randomly assigned to one of the four weaning techniques. The median duration of weaning was 5 days for intermittent mandatory ventilation, 4 days for pressure-support ventilation, 3 days for intermittent trials of spontaneous breathing, and 3 days for a once-daily trial of spontaneous breathing. After adjusting for covariates, the rate of successful weaning was significantly higher with a once-daily trial of spontaneous breathing compared to intermittent mandatory ventilation (rate ratio, 2.83; P<0.006) and pressure-support ventilation (rate ratio, 2.05; P<0.04). There was no significant difference in the rate of success between once-daily trials and multiple daily trials of spontaneous breathing. The study concluded that a once-daily trial of spontaneous breathing led to extubation about three times faster than intermittent mandatory ventilation and twice as fast as pressure-support ventilation. Multiple daily trials of spontaneous breathing were equally successful.