"Purpose: Hospital-acquired pressure injuries are a serious problem among critical care patients. To compare pressure-reducing foam mattresses with standard hospital foam mattresses in the prevention of pressure injury in patients under mechanical ventilation in a respiratory care center.Method: This was a quasi-experimental study in the respiratory care center of a university hospital in Taiwan from January 2017 to June 2018. Sixty bedridden patients under mechanical ventilation at risk of developing pressure injury were according to a 1:1 ratio to pressure-reducing foam mattress or standard hospital foam mattress groups under the same context of standard care for 21 days. Primary endpoints were the mean total Braden scale score and the incidence of a new pressure injury of at least Category or Stage II during the study period.Results: Primary endpoints were not significant different between the two groups at baseline and at the end of the study. However, the pressure-reducing foam mattress group had statistically significant higher comfort scores (p < 0.001) and sleep quality scores (p < 0.001) than did the standard hospital foam mattress group.Conclusions: Mechanically ventilated patients on standard hospital foam mattresses had a tendency to develop more pressure injury. 2-hour turning schedule may have compensated for the absence of the pressure-reducing foam mattress for the patients under mechanical ventilation. Pressure-reducing foam mattresses improved the scores of comfort and sleep quality."