BACKGROUND: The current technology of high-velocity nasal insufflation (HVNI) can be equipped with an oxygen assist module (OAM) that continuously monitors and automatically adjusts the inspired oxygen fraction (FiO METHODS: This randomized crossover study enrolled 16 mechanically ventilated subjects who were ready to wean. The subjects were randomized to protocol A (HVNI with OAM for 60 min, followed by conventional HVNI for another 60 min) or protocol B (conventional HVNI for 60 min, followed by HVNI with OAM for another 60 min) after extubation. In HVNI with OAM, the target SpO RESULTS: HVNI with OAM significantly maintained SpO CONCLUSIONS: HVNI with OAM can maintain SpO TRIAL REGISTRATION: This study was registered in the Thai Clinical Trial Registry (TCTR20220801007) before the inclusion of the first patient.