The current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in intensive care unit are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).An international, multicentre, prospective cohort study of patients presenting with hypoxemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with PaO2/FiO2 ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure (PEEP) of at least 5 cm H2O. ICU prevalence, causes of hypoxemia, hospital survival, factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (8.2%, CHF). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1%versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality but similar adjusted mortality than ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only 2 quadrants involved.More than one third of the patients receiving mechanical ventilation have hypoxaemia and new infiltrates with an hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.