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Background/Objectives: Pressure injuries (PIs), a recognized indicator of care quality, have a higher incidence in intensive care units (ICUs). Our objective was to assess whether critically ill patients identified as “unprotected” (COMHON ≥ 11) developed pressure injuries despite additional preventive measures. Methods: A historical cohort study of an adult ICU was carried out. Of the 811 patients admitted in 2022, 400 were selected. All of them were subjected to the ICU’s PI Prevention Protocol, and those with a moving average of the COMHON Index ≥ 11 were given two additional measures: a multilayer dressing on the sacrum, and anti-equinus and heel-pressure-relieving boots. Results: A total of 36 patients presented with PIs (cumulative incidence of 9%). Significant differences were observed in their mean length of stay and in their disease severity score (APACHE-II). Most of the PIs were located on the sacrum, followed by the heel. Prior to the appearance of the PIs, a sacral dressing was applied to 100% of the patients, while anti-equinus and heel-pressure-relieving boots were only applied to 58.3%. Of the 36 patients with PIs, 52.8% had a PI on the sacrum and 22.2% on the heel. Conclusions: Focusing only on those who presented with PIs, we observed that the considered measures were not effective for preventing PIs in all the patients. Not all PIs are preventable, and individual risk factors should be considered. In the future, we will analyze the individual characteristics of these patients and verify whether the Prevention Protocol was followed, in order to determine how they could have been prevented or whether they were so-called unavoidable PIs. Full article