Humidification of inspired gas is critical in ventilated patients, usually achieved by heat and moisture exchange devices (HMEs). HME and the endotracheal tube (ETT) add airflow resistance. Ventilated patients are sometimes treated in hyperbaric chambers. Increased gas density may increase total airway resistance, peak pressures (PPs), and mechanical work of breathing (WOB). We tested the added WOB imposed by HMEs and various sizes of ETT under hyperbaric conditions. We mechanically ventilated 4 types of HMEs and 3 ETTs at 6 minute ventilation volumes (7-19.5 L/min) in a hyperbaric chamber at pressures of 1 to 6 atmospheres absolute (ATA). Peak pressure increased with increasing chamber pressure with an HME alone, from 2 cm H₂O at 1 ATA to 6 cm H₂O at 6 ATA. Work of breathing was low at 1 ATA (0.2 J/L) and increased to 1.2 J/L at 6 ATA at minute ventilation = 19.5 L/min. Connecting the HME to an ETT increased PP as a function of peak flow and chamber pressure. Reduction of the ETT diameter (9 > 8 > 7.5 mm) and increase in chamber pressure increased the PP up to 27.7 cm H₂O, resistance to 33.2 cmH₂O*s/L, and WOB to 3.76 J/L at 6 ATA with a 7.5-mm EET. These are much greater than the usually accepted critical peak pressures of 25 cm H₂O and WOB of 1.5 to 2.0 J/L. Endotracheal tubes less than 8 mm produce significant added WOB and airway pressure swings under hyperbaric conditions. The hyperbaric critical care clinician is advised to use the largest possible ETT. The tested HMEs add negligible resistance and WOB in the chamber.