IntroductionHypoxemia and hyperoxia may occur after surgery with potential related complications. The FreeO₂PostOp trial is a prospective, multicentre, randomised controlled trial that evaluates the clinical impact of automated O₂administration versus conventional O₂therapy after major abdominal or thoracic surgeries. The study is powered to demonstrate benefits of automated oxygen titration and weaning in term of oxygenation, which is an important surrogate for complications after such interventions.Methods and analysisAfter extubation, patients are randomly assigned to theStandard(manual O₂administration) orFreeO₂group (automated closed-loop O₂administration). Stratification is performed for the study centre and a medical history of chronic obstructive pulmonary disease (COPD). Primary outcome is the percentage of time spent in the target zone of oxygen saturation, during a 3-day time frame. In both groups, patients will benefit from continuous oximetry recordings. The target zone of oxygen saturation is SpO₂=88%–92% for patients with COPD and 92%–96% for patients without COPD. Secondary outcomes are the nursing workload assessed by the number of manual O₂flow adjustments, the time spent with severe desaturation (SpO₂<85%) and hyperoxia area (SpO₂>98%), the time spent in a hyperoxia area (SpO₂>98%), the VO₂, the duration of oxygen administration during hospitalisation, the frequency of use of mechanical ventilation (invasive or non-invasive), the duration of the postrecovery room stay, the hospitalisation length of stay and the survival rate.Ethics and disseminationThe FreeO₂PostOp study is conducted in accordance with the declaration of Helsinki and was registered on 11 September 2015 (http://www.clinicaltrials.gov). First patient inclusion was performed on 14 January 2016. The results of the study will be presented at academic conferences and submitted to peer-reviewed journals.Trial registration numberNCT02546830.