Background: Noninvasive respiratory support (NIRS) has been extensively used during the COVID-19 surge for patients with acute respiratory failure. However, little data are available about barotrauma during NIRS in patients treated outside the intensive care unit (ICU) setting. Methods: COVIMIX-2 was an ancillary analysis of the previous COVIMIX study, a large multicenter observational work investigating the frequencies of barotrauma (i.e., pneumothorax and pneumomediastinum) in adult patients with COVID-19 interstitial pneumonia. Only patients treated with NIRS outside the ICU were considered. Baseline characteristics, clinical and radiological disease severity, type of ventilatory support used, blood tests and mortality were recorded. Results: In all, 179 patients were included, 60 of them with barotrauma. They were older and had lower BMI than controls (p< 0.001 andp= 0.045, respectively). Cases had higher respiratory rates and lower PaO2/FiO2(p= 0.009 andp< 0.001). The frequency of barotrauma was 0.3% [0.1–1.3%], with older age being a risk factor for barotrauma (OR 1.06,p= 0.015). Alveolar-arterial gradient (A-a) DO2was protective against barotrauma (OR 0.92 [0.87–0.99],p= 0.026). Barotrauma required active treatment, with drainage, in only a minority of cases. The type of NIRS was not explicitly related to the development of barotrauma. Still, an escalation of respiratory support from conventional oxygen therapy, high flow nasal cannula to noninvasive respiratory mask was predictive for in-hospital death (OR 15.51,p= 0.001). Conclusions: COVIMIX-2 showed a low frequency for barotrauma, around 0.3%. The type of NIRS used seems not to increase this risk. Patients with barotrauma were older, with more severe systemic disease, and showed increased mortality.