During conventional intermittent mandatory ventilation (IMV) in neonates, asynchrony between mechanical and spontaneous breaths is frequent. We tested the hypothesis that patient-triggered ventilation (PTV) reduces the work of breathing (WOB) by providing synchronized assistance for each breath. Accordingly, six intubated preterm infants were studied at the median postnatal age of 34 days while they were being weaned from mechanical ventilation (MV). Patients were ventilated using the Draeger Babylog 8000 (software #3) and studied in four successive modes of MV with a constant level of positive end-expiratory pressure. They were randomly assigned to IMV, PTV with peak inspiratory pressure of either 10 cm H2O (PTV10) or 15 cm H2O (PTV15), and spontaneous ventilation with continuous positive airway pressure. PTV was achieved in the assist/control mode. During PTV, infants adapted their pattern of breathing in response to an increase in tidal volume (median 7.5 ml/kg in IMV versus 8.2 in PTV10 and 8.5 in PTV15, p<0.05) by decreasing their respiratory rate, thus maintaining minute ventilation (439 ml/min/kg in IMV versus 422 in PTV10 and 455 in PTV15, NS) and transcutaneous CO2. WOB fell significantly during PTV compared with its level during IMV (0.81 J/L in IMV versus 0.48 and 0.47 during PTV10 and PTV15, respectively, p<0.05). Power of breathing decreased in the same proportions. These results demonstrate that PTV mode allows reduction of the workload imposed on the respiratory muscles.