Prevention of pressure injuries (PI) is a public health issue. Among the preventive measures, the use of support surfaces adapted to the risk of PI occurrence is recommended. This study aimed to report the incidence of PIs in patients at medium-to-high risk of occurrence of PIs and using a new non-motorised automated decompression air mattress combined with other recommended PI prevention measures. An observational, national, multicentre, prospective, non-comparative study, with a follow-up period of 35 days was conducted. Patients at medium-to-high risk of PIs and without PIs at baseline were included if they were lying on a specific non-powered automated decompression air mattress. The primary outcome was the percentage of patients who developed at least one category 2 or more severe PI of the sacrum, backbone or heel between day 0 and day 35. In total, 81 patients were included from four participating centres. There was one report of a patient with a PI that fitted within the definition of the primary outcome, meaning an incidence of 1.2% (95% confidence interval (CI) 0-6.7%). More than 80% of patients rated the overall comfort and the stability of the non-motorised automated decompression air mattress as satisfactory or very satisfactory. In more than 80% of cases, the healthcare teams found the use of the mattress to be easy or very easy. This study has shown that in combination with other preventive measures, the use of a specific non-motorised air mattress with automated decompression is associated with a low incidence of PIs in patients with medium-to-high risk of occurrence of PIs.