INTRODUCTION: The safest oxygen levels needed for preterm infant respiratory support at birth are uncertain. We aimed to compare the outcomes of infants up to 28 METHODS: This randomised controlled phase III trial was stratified by (1) site, (2) gestation and (3) multiplicity. Infants between 23+0 to 28+6 weeks gestation were randomised to initial respiratory support with FiO PRIMARY OUTCOME: Survival to 36 weeks gestation without documented brain injury. ASSESSMENTS: FiO STATISTICAL ANALYSIS PLAN: Assuming 32% of infants would die or survive with brain injury by 36 weeks, 735 infants per arm (1470 total) were needed to detect a risk difference of 8% (25% relative risk reduction), with 10% non-adherence to protocol, 85% β and 5% α. ETHICS: Approved by the John Hunter Human Research Ethics Committee (2019/ETH/3837) for waiver of consent for all Australian sites for randomised allocation and primary outcome. CONCLUSION: Recruitment started in 2018 and was achieved on 30 September 2024. The Data and Safety Committee review found no major safety concerns at 50% recruitment. TRIAL REGISTRATION NUMBER: ACTRN 12618000879268.