Oxygen is commonly administered in hospitals, with poor adherence to treatment recommendations.We conducted a multicentre randomised controlled study in patients admitted to the emergency department requiring O ≥3 L·min Patients were randomised to automated closed-loop or manual O titration during 3 h. Patients were stratified according to arterial carbon dioxide tension ( ) (hypoxaemic ≤45 mmHg; or hypercapnic >45-≤55 mmHg) and study centre. Arterial oxygen saturation measured by pulse oximetry ( ) goals were 92-96% for hypoxaemic, or 88-92% for hypercapnic patients. Primary outcome was % time within target. Secondary endpoints were hypoxaemia and hyperoxia prevalence, O weaning, O duration and hospital length of stay.187 patients were randomised (93 automated, 94 manual) and baseline characteristics were similar between the groups. Time within the target was higher under automated titration (81±21% 51±30%, p<0.001). Time with hypoxaemia (3±9% 5±12%, p=0.04) and hyperoxia under O (4±9% 22±30%, p<0.001) were lower with automated titration. O could be weaned at the end of the study in 14.1% 4.3% patients in the automated and manual titration group, respectively (p<0.001). O duration during the hospital stay was significantly reduced (5.6±5.4 7.1±6.3 days, p=0.002).Automated O titration in the emergency department improved oxygenation parameters and adherence to guidelines, with potential clinical benefits.