OBJECTIVE To compare pressure injury (PI) incidence based on repositioning intervals and support surfaces in acute care settings. METHODS This pragmatic, quasi-experimental trial recruited a total of 251 critically ill patients who were at low or moderate risk for PI development. Participants were assigned to three interventions: a 2-hour repositioning interval using an air mattress, a 2-hour repositioning interval using a foam mattress, or a 3-hour repositioning interval using a foam mattress. Data were collected by nurses every shift over the course of 14 days. Pressure injury incidence was analyzed using a χ 2 test. RESULTS There were no statistically significant differences in PI incidence between the groups with a 2-hour repositioning interval. However, the PI incidence in the group using a foam mattress with a 3-hour repositioning interval was significantly lower than in the group using an air mattress with a 2-hour repositioning interval (odds ratio, 0.481; 95% confidence interval, 0.410–0.565). CONCLUSIONS The findings showed that PIs decreased when the repositioning interval was extended from every 2 hours to every 3 hours while using foam mattresses. This study suggests that a 3-hour repositioning interval using a foam mattress could be applied to reduce the risk of PI development for patients at low or moderate risk.