Background: Older patients are more susceptible to developing COVID-19, progressing to ARDS. Prone positioning (PP) is recommended worldwide for severe ARDS. However, its response in older patients remains poorly understood. Aim: to evaluate the predictive of oxygenation response (OR) and mortality among older patients exposed to PP due to ARDS-COVID-19. Methods: This retrospective multicenter cohort study enrolled 223 patients aged ?65 who received PP sessions for severe ARDS due to COVID-19 using invasive mechanical ventilation. The PaO2/FiO2 ratio was used to assess the OR. Patients were divided according to OR, based on a 20-point improvement in PaO2/FiO2. Analyzed data was obtained by electronic medical record and included demographic data, comorbidities, SAPS III, SOFA, complications, ventilator settings, and respiratory mechanics calculations. Mortality was defined as deaths that occurred until hospital discharge. Results: The average age was 72 (68-76) y/o, 134 (60.1%) were male, and most patients had arterial hypertension (164 [73.5%]). The non-responders group had a higher SAPS III score (78 [66-86] vs. 72 [56-79]; p=0.011) and a higher incidence of complications (12 [19.7%] vs. 3 [1.9%]; p<0.001). No difference was found in the mortality rate. A lower SAPS III predicted OR (OR= 0.97 [0.94-0.99]; p=0.02), and the male sex predicted mortality (OR=0.21 [0.06-0.70]; p=0.01). Conclusion: These findings suggest that previous health status predicts the oxygenation response while the male sex predicts mortality among older patients with severe COVID-19-ARDS subjected to  PP.