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Background Early application of prolonged prone positioning has been shown to improve patient survival in moderate to severe adult respiratory distress syndrome (ARDS) patients. Prone position is a key component of lung protective mechanical ventilation in association with low tidal volume and neuromuscular blocking agents in patients with severe ARDS. Pressure sores are the major prone position complication. The rate of complication is lowering with the increase in center expertise. Aims The aim of this study was to examine the onset of pressure sores and other complications caused by the use of prone position in patients having ARDS. Design This is a single-center, retrospective, observational study. Results One hundred seventy patients were enrolled, with a median age of 49 years (interquartile range [IQR], 38-63). Of all participants, 58% (n = 98) survived the intensive care unit recovery. The total prone position maneuvers were 526, with a median of 2 prone position sessions for each patient (IQR, 1-3). The median length of the prone position session was 9 hours (IQR, 7-12). Twenty-three patients developed pressure sores after prone position (14%). The anatomical positions of pressure sores were as follows: face/chin, 5% (n = 8); face/cheekbones, 6% (n = 11); thorax, 2% (n = 3); trochanter, 1% (n = 1); and other sites, 5% (n = 8). Complications were observed in 1% (n = 6) of all pronation maneuvers (vomit, 2%; respiratory device removal, 0.4%). No removal of intravascular catheter was observed. Conclusions The onset rate of complications given by the use of prone position in ARDS patients is similar to data reported by previous literature. The implementation of a dedicated protocol in specialized centers and the involvement of 5 trained and skilled professionals while moving the patient in the prone position are recommended to prevent the occurrence of similar adverse events.