Synchronized patient-triggered ventilation in neonates has become a more common practice in the intensive care nursery. Infant ventilators are now capable of performing synchronized intermittent mandatory ventilation (SIMV) as well as assist-control (AC). Conflicting data exist regarding the efficacy and safety of these modes. The purpose of this study was to compare AC and SIMV to intermittent mandatory ventilation (IMV) in neonates with respiratory distress syndrome. Methods: Eleven patients (BW 1273 ± 606g, GA 28.3±3.8 wks) received AC, SIMV and IMV ventilation by random sequence for 2 hours per mode (VIP BIRD, Palm Springs, CA). Continuous pulmonary function monitoring was measured using a plethysmographic technique(Vitaltrends, Wallingford, CT) and arterial blood gases were obtained at the end of each mode. Ventilator pressure settings were kept constant. Percent synchrony was determined by analysis of synchrony curves with the investigator blinded to the mode of ventilation. Data were analyzed by one-way ANOVA. Results: Both SIMV and AC modes showed a greater percent synchrony compared to IMV (98± 0.03 and 98± 0.03 vs. 81±0.15% respectively, p<0.01). Tidal volume delivered during SIMV was significantly greater compared to IMV (5.4 ± 2.5 vs. 4.4 ± 1.74 cc/kg, p=.04). A lower pCO2 was also found during SIMV compared to IMV(44.7±6.5 vs. 49.8±8.3mmHg), however this fell short of significance (p=0.14). There was no difference in tidal volume delivered between AC and the other two modes. In addition, pCO2 was lower during AC compared to IMV(40.8±6.4 vs. 49.8±8.3 mmHg, p=0.014). Conclusions: Over a 2 hour time interval these data showed 1) patient-triggered ventilation improves synchrony, 2) SIMV delivers higher tidal volumes as compared to IMV, and 3) AC improves alveolar ventilation as compared to IMV but there was no advantage provided by AC vs. SIMV. Further studies are needed to investigate the long term effects of patient-triggered ventilation.