PURPOSE:: IntelliVent-ASV is a development of adaptive support ventilation (ASV) that automatically adjusts ventilation and oxygenation parameters. This study assessed the safety and efficacy of IntelliVent-ASV in sedated intensive care unit (ICU) patients with acute respiratory failure. METHODS:: This prospective randomized crossover comparative study was conducted in a 12-bed ICU in a general hospital. Two periods of 2 h of ventilation in randomly applied ASV or IntelliVent-ASV were compared in 50 sedated, passively ventilated patients. Tidal volume (V T), respiratory rate (RR), inspiratory pressure (P INSP), SpO2 and ETCO2 were continuously monitored and recorded breath by breath. Mean values over the 2-h period were calculated. Respiratory mechanics, plateau pressure (P PLAT) and blood gas exchanges were measured at the end of each period. RESULTS:: There was no safety issue requiring premature interruption of IntelliVent-ASV. Minute ventilation (MV) and V T decreased from 7.6 (6.5–9.5) to 6.8 (6.0–8.0) L/min (p < 0.001) and from 8.3 (7.8–9.0) to 8.1 (7.7–8.6) mL/kg PBW (p = 0.003) during IntelliVent-ASV as compared to ASV. P PLAT and FiO2 decreased from 24 (20–29) to 20 (19–25) cmH2O (p = 0.005) and from 40 (30–50) to 30 (30–39) % (p < 0.001) during IntelliVent-ASV as compared to ASV. RR, P INSP, and PEEP decreased as well during IntelliVent-ASV as compared to ASV. Respiratory mechanics, pH, PaO2 and PaO2/FiO2 ratio were not different but PaCO2 was slightly higher during IntelliVent-ASV as compared to ASV. CONCLUSIONS:: In passive patients with acute respiratory failure, IntelliVent-ASV was safe and able to ventilate patients with less pressure, volume and FiO2 while producing the same results in terms of oxygenation.