BACKGROUND: Noninvasive ventilation (NIV) has been recognized as an effective strategy in preventing endotracheal intubation in subjects with acute respiratory failure (ARF). Some interface-related complications have also been recognized, such as skin breakdown (SB). The aim of this study was to determine the frequency of SB and identify potential treatment-related risk factors for its development in adults with ARF undergoing NIV or CPAP. METHODS: A cross-sectional study was conducted in a general hospital. Subjects were retrospectively enrolled in this study if they were > 18 y old and developed ARF caused by any condition in which NIV or CPAP was indicated for at least one application for a period longer than 2 h. The outcomes were the prevalence of SB and the evaluation of related risk factors. Data were extracted from the electronic medical records. A stepwise forward logistic regression model was used to identify independent risk factors for SB development. RESULTS: A total of 375 subjects (160 males) met the inclusion criteria and were enrolled in the study. Fifty-four subjects (14.4%) developed SB. The mean number of applications of NIV or CPAP carried out for > 2 h was higher in subjects with SB (7.1 ؎ 13.3 h) than in those without SB (4.4 ؎ 13.3 h) (P ‫؍‬ .03). Subjects with SB also presented a higher total duration of NIV use (44.6 ؎ 118.5 h) compared with subjects without SB (21.8 ؎ 45.5 h) (P ‫؍‬ .01). Subjects who developed SB presented a higher use of oronasal mask (92.6%) compared with the group that did not (21.5%) (P < .001). CONCLUSIONS: In patients with ARF undergoing NIV or CPAP, oronasal mask use for > 26 h was independently associated with development of SB.