Abstract Background: Elderly patients are more susceptible to Coronavirus Disease-2019 (COVID-19) and are more likely to develop it in severe forms, (e.g., Acute Respiratory Distress Syndrome [ARDS]). Prone positioning is a treatment strategy for severe ARDS; however, its response in the elderly population remains poorly understood. The main objective was to evaluate the predictive response and mortality of elderly patients exposed to prone positioning due to ARDS-COVID-19. Methods: This retrospective multicenter cohort study involved 223 patients aged ≥ 65 years, who received prone position sessions for severe ARDS due to COVID-19, using invasive mechanical ventilation. The PaO2/FiO2 ratio was used to assess the oxygenation response. The 20-point improvement in PaO2/FiO2 after the first prone session was considered for good response. Data were collected from electronic medical records, including demographic data, laboratory/image exams, complications, comorbidities, SAPS III and SOFA scores, use of anticoagulants and vasopressors, ventilator settings, and respiratory system mechanics. Mortality was defined as deaths that occurred until hospital discharge. Results: Most patients were male, with arterial hypertension and diabetes mellitus as the most prevalent comorbidities. The non-responders group had higher SAPS III and SOFA scores, and a higher incidence of complications. There was no difference in mortality rate. A lower SAPS III score was a predictor of oxygenation response, and the male sex was a risk predictor of mortality. Conclusion: The present study suggests the oxygenation response to prone positioning in elderly patients with severe COVID-19-ARDS correlates with the SAPS III score. Furthermore, the male sex is a risk predictor of mortality.