Objective. To determine whether a ventilatory strategy of permissive hypercapnia (PHC) reduces the duration of assisted ventilation in surfactant- treated neonates weighing 601 to 1250 g at birth. Design. Forty-nine surfactant-treated preterm infants (birth weight: 854 ± 163 g; gestational age: 26 ± 1.4 weeks) receiving assisted ventilation were randomized during the first 24 hours of age to a PHC group (Paco2: 45-55 mm Hg) or to a normocapnia group (NC; Paco2: 35-45 mm Hg). The primary outcome measure was the total number of days on assisted ventilation. Uniform extubation and reintubation criteria were used for both groups. All patients received aminophylline before extubation. Results. The total number of days on assisted ventilation expressed as median (25th-75th percentiles) was 2.5 (1.5-11.5) in the PHC group and 9.5 (2.0-22.5) in the NC group (Mann-Whitney U test). The number of patients on assisted ventilation throughout the first 96 hours after randomization was lower in the PHC group (log rank test). During that period, the ventilated patients in the PHC group had a higher Paco2 and lower peak inspiratory pressure, mean airway pressure, and ventilator rate than did those in the NC group. The percentage of patients requiring reintubation within 24 hours postextubation (PHC 17% vs NC 28%) and supplemental oxygen at 28 days of life (PHC 43% vs NC 64%) and the total days of oxygen supplementation (PHC 15 [4-53] vs NC 32 [17-50]) did not differ between the groups. There were no differences in mortality, air leaks, intraventricular hemorrhage; periventricular leukomalacia, retinopathy of prematurity, or patent ductus arteriosus. Conclusion. A ventilatory strategy of PHC in preterm infants who receive assisted ventilation is feasible, seems safe, and may reduce the duration of assisted ventilation.