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Acute hypoxemic respiratory failure (RF) occurs frequently in critically ill patients and is associated with substantial morbidity, mortality and resource use. We developed a comprehensive machine-learning–based monitoring system to support ICU physicians in managing RF through early detection, continuous monitoring, assessment of extubation readiness, and prediction of extubation failure (EF). In study patients, the model predicted 80% of RF events with 45% precision, identifying 65% of events more than 10 hours before, significantly outperforming standard clinical monitoring based on oxygenation index. The model was successfully validated in an external ICU cohort. We also demonstrated how predicted EF risk could help prevent extubation failure and unnecessarily prolonged ventilation. Lastly, we illustrated how prediction of RF risk, along with ventilator need and extubation readiness, helped ICU resource planning for mechanical ventilation. Our model predicted ICU-level ventilator demand 8–16 hours ahead, with a mean absolute error of 0.4 ventilators per 10 patients.