This study explored the use of high-flow nasal oxygen (HFNO) in both pre-oxygenation and apnoeic oxygenation in adults who were intubated following a non-rapid sequence induction. Fifty patients were randomised to receive pre-oxygenation via a standard facemask or the Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) device. After five minutes of pre-oxygenation, induction and muscle relaxant agents were given. While waiting for complete paralysis, patients in the standard facemask group received bag-mask ventilation (BMV), whereas patients in the HFNO group received apnoeic oxygenation via the THRIVE device. Serial blood samples for arterial blood gas analysis were taken. Baseline patient and airway characteristics were similar. The median PaO2 after pre-oxygenation was 357 (interquartile range [IQR] 324-450 [range 183-550]) mmHg in the facemask group, compared to 471 (IQR 429-516 [range 185-550]) mmHg in the HFNO group (P=0.01). The median arterial partial pressure of oxygen (PaO2) in the HFNO group decreased after a period of apnoeic oxygenation, and was significantly lower when compared to patients who received BMV in facemask group. The arterial carbon dioxide partial pressure (PaCO2) level after complete paralysis was significantly higher in the HFNO group when compared to the facemask group (median 52 [IQR 48-55 {range 40-65}] versus median 43 [IQR 40-48 {range 35-63}] mmHg, P=0.0005 and P=0.004 respectively). There were no differences in the time to muscle paralysis and time to intubation. Seven patients required use of airway adjuncts during BMV in the facemask group, compared to none in the HFNO group (P=0.004). No complications were observed in either group. HFNO produces a higher PaO2 after pre-oxygenation and safe PaO2 during intubation. However, the subsequent fall in PaO2 and rise in PaCO2 indicates that it is not as effective as BMV in maintaining oxygenation and ventilation following neuromuscular blockade.