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Introduction We designed the Optimising Care in Critically Ill at the UCHealth by Liberalising the Target O₂ in Mechanically ventilated intensive care unit (ICU) Patients to determine the effectiveness of a multimodal educational and electronic health record order panel intervention in limiting occult hypoxaemia and hyperoxaemia in patients receiving invasive mechanical ventilation by targeting a prespecified oxygen saturation (S pO₂ 90%–96%) range.Methods and analysis This trial is a pragmatic electronic health record-embedded, multisite, cluster-randomised, stepped-wedge implementation of a multimodal educational and electronic health record order panel intervention aimed at achieving a standardised intermediate target range of S pO₂ (90%–96%) or partial pressure of oxygen (PaO₂ 60–100 mm Hg) in mechanically ventilated adult patients admitted to the ICU across a 10 hospital health system that includes a large academic centre and smaller community hospitals.The primary endpoint is ventilator-free days to day 30, defined as the number of days alive and not receiving support through invasive mechanical ventilation following the first initiation of invasive mechanical ventilation in a participating ICU during the hospitalisation. Secondary outcomes include a variety of clinical endpoints: hospital-free days to day 30, all-cause mortality to day 90, need for supplemental oxygen at discharge and incidence of occult hypoxaemia and hypoxaemia. We will analyse primary and secondary endpoints using a mixed effects modelling framework, with specific distributions chosen depending on the type of outcome (eg, binary, count, ordinal, time-to-event).Ethics and dissemination Research is performed under a waiver of informed consent for minimal-risk research, as approved by Colorado Multiple Institutional Review Board (24-0065). Results will be disseminated in peer-reviewed publications and at national and international conferences.Trial registration number NCT06501118.