OBJECTIVE: To evaluate the ability of a computer-driven system (CDS) to manage pressure-support ventilation over prolonged periods and to predict weaning readiness compared to intensivists. The system continuously adapts pressure support, gradually decreases ventilatory assistance when possible, and indicates weaning readiness. DESIGN AND SETTING: A two-center, prospective, open, clinical, pilot study in medical ICUs of two university hospitals. PATIENTS AND PARTICIPANTS: 42 consecutive mechanically ventilated patients (60+/-14 years, SAPS II 39+/-15), 9 of whom were excluded. INTERVENTIONS: As soon as patients could tolerate pressure support, they were ventilated with the CDS. The times of weaning readiness determined by the intensivists and CDS were compared. MEASUREMENTS AND RESULTS: Weaning was successful in 25 patients and failed in 7; unplanned extubation occurred in 1 patient. Time on CDS ventilation was 3+/-3 days (maximum, 12 days). The CDS detected weaning readiness earlier than the intensivists in 17 patients, and intensivists earlier than the CDS in 4; in 11 patients detection times coincided. CONCLUSIONS: A CDS was successful in fully managing pressure-support ventilation over prolonged periods and often proposed weaning readiness earlier than the intensivists did. Use of this CDS may reduce the duration of mechanical ventilation.