ObjectiveIn adult patients with acute respiratory failure, nasal high-flow (NHF) therapy at the time of intubation can decrease the duration of hypoxia. The objective of this pilot study was to calculate duration of peripheral oxygen saturation below 75% during single and multiple intubation attempts in order to inform development of a larger definitive trial.Design and settingThis double-blinded randomised controlled pilot trial was conducted at a single, tertiary neonatal centre from October 2020 to October 2021.ParticipantsInfants undergoing oral intubation in neonatal intensive care were included. Infants with upper airway anomalies were excluded.InterventionsInfants were randomly assigned (1:1) to have NHF 6 L/min, FiO21.0 or NHF 0 L/min (control) applied during intubation, stratified by gestational age (<34 weeks vs ≥34 weeks).Main outcome measuresThe primary outcome was duration of hypoxaemia of <75% up to the time of successful intubation,Results43 infants were enrolled (26 <34 weeks and 17 ≥34 weeks) with 50 intubation episodes. In infants <34 weeks’ gestation, median duration of SpO2of <75% was 29 s (0–126 s) vs 43 s (0–132 s) (p=0.78, intervention vs control). Median duration of SpO2 of<75% in babies ≥34 weeks’ gestation was 0 (0–32 s) vs 0 (0–20 s) (p=0.9, intervention vs control).ConclusionThis pilot study showed that it is feasible to provide NHF during intubation attempts. No significant differences were noted in duration of oxygen saturation of <75% between groups; however, this trial was not powered to detect a difference. A larger, higher-powered blinded study is warranted.