High-flow nasal cannula (HFNC) systems are increasingly used for patients with both acute and chronic respiratory failure because of the clinical effectiveness and patient comfort associated with their use. Recently, HFNC has been used not only as a respiratory support device, but also as a drug delivery system. HFNC is designed to administer heated and humidified inspiratory oxygen flows (100% relative humidity at 37°C). Therefore, HFNC can provide high flows (up to 60 L/min) without discomfort. Moreover, HFNC improves oxygenation by exerting physiologic effects such as (a) dead-space washout and (b) moderate positive airway pressure. These characteristics and physiologic effects of HFNC may permit administration of high-flow nitrous oxide sedation while ensuring patient comfort and adequate sedative effect.