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BACKGROUND: A recent study found that activation of disconnection and low-pressure alarms is common during mouthpiece ventilation and may represent a major limitation to its use. The aim of this bench study was: (1) to investigate the technical aspects that can influence the setting of the ventilator during mouthpiece ventilation and (2) to provide a practical setting strategy to avoid the alarm activation. METHODS: Eight life-support ventilators able to deliver volume controlled ventilation were tested in a bench study using a single-limb non-vented circuit configuration connected to a standard mouthpiece. Disconnection and apnea alarm were turned off or set at the least sensitive setting. The backup frequency was set at the lowest available level. Different tidal volumes (VT) (from 500 to 1,200 mL) were tested with the rectangular and descending flow shape. For each VT, we reported the maximum set inspiratory time (TI) that allowed preventing activation of the low-pressure alarm. The presence of auto-triggering was also surveyed. RESULTS: We found that a correct combination of VT and TI avoided the activation of disconnection and low-pressure alarms in all but 3 ventilators. One ventilator did not allow mouthpiece ventilation independently from the settings used. The inability to turn off the apnea alarm in two other ventilators led to the alarm going off in any tested conditions after 120 s without triggered breaths. Auto-triggering was seldom found and easily worked out, except for in one ventilator. CONCLUSIONS: An appropriate alarm setting and combination of VT and TI would allow the majority of the tested ventilators to be used for mouthpiece ventilation without alarm activation.