A variety of ventilators are used in the NICU. Ventilator and lung function measures are often applied in weaning protocols or as outcome variables. The effect of different ventilators on these measures has not been well studied. Our objective was to compare ventilator and lung function measurements in a chronic preterm animal model managed with two different neonatal ventilators. Timed baboon pregnancies exposed to antenatal steroids were delivered by C/S at 125 days (term = 185 days). Infants were immediately intubated, given surfactant, and ventilated with low tidal volumes (4-6 ml/kg) for 6-14 days using well-defined protocols. One group was ventilated via InfantStar (IS) and the other by VIP-Bird (VIP). Physiologic and pulmonary function data were serially recorded with the VitalTrends plethysmography system. Between ventilator comparisons were made. InfantStar (IS) was used on 22 infants in 2002-03, VIP was used on 29 infants in 2004-05. No differences were found for gestation, birth weight, gender, paO(2), paCO(2), FiO(2), arterial/alveolar ratio, dynamic compliance, inspiratory resistance, or tidal volumes. From 24 to 336 h, peak and mean airway pressure, ventilator rate, and ventilatory efficiency index (VEI: PIP x R x CO(2)/1,000) were significantly greater in the VIP group at multiple time points. VIP use was associated with a significant increase in expiratory airway resistance (Rexp - cmH(2)O/L/s) at all but one-time points studied. Compared to the IS, use of the VIP-Bird ventilator in surfactant treated immature baboons with RDS was associated with increased expiratory airway resistance and indices of impaired ventilation, but not oxygenation. Ventilator management in the NICU, especially weaning, may be affected by the specific ventilator in use.