"Purpose: To compare the effectiveness of pressure relief pads in preventing bi-level positive airway pressure-related injuries by analyzing data from a medical reporting database. Methods: The authors took a convenience sample of records from the medical reporting database of the adult medical intensive care unit of a regional teaching hospital in southern Taiwan. Secondary database analysis was employed to examine the effectiveness of pressure relief pads in preventing pressure injuries. Results: The incidence of pressure-related injuries in the pressure relief pads group was 6.06%, whereas the incidence in the no relief pads group was 7.78% (p = .5863). Pressure relief pads delayed the occurrence of pressure injuries by 21.18 hours (p = .8660), reduced the number of pressure injury lesions by 0.12 (p = .5501), reduced the surface area of pressure injuries by 1.96 cm2 (p = .7334), and reduced the risk of severe pressure injury (risk ratio = 0.44, p = .1666). Due to the small number of clinical incident pressure injuries reported, the comparison of effectiveness did not reach statistical significance. Conclusion: Although no significant difference was observed between the two groups, real-world data from the secondary database revealed that the pressure relief pads effectively and safely prevented pressure injuries.