Background: Facemask ventilation is routinely used to preoxygenate patients before endotracheal intubation during anesthesia induction or to secure ventilation in patients with respiratory insufficiency. Occasionally, facemask ventilation cannot be performed adequately. The placement of a regular endotracheal tube through the nose into the hypopharynx may be a valid alternative to improve ventilation and oxygenation before endotracheal intubation (nasopharyngeal ventilation). We tested the hypothesis that nasopharyngeal ventilation is superior in its efficacy compared to traditional facemask ventilation.Methods: In this prospective, randomized, crossover trial, we enrolled surgical patients requiring either nasal intubation (cohort #1, n = 20) or patients who met “difficult to mask ventilate” criteria (cohort #2, n = 20). Patients in each cohort were randomly assigned to receive pressure-controlled facemask ventilation followed by nasopharyngeal ventilation or vice versa. The ventilation settings were kept constant. The primary outcome was tidal volume. The secondary outcome was the difficulty of ventilation, measured using the Warters grading scale.Results: Tidal volume was significantly increased by nasopharyngeal ventilation in cohort #1 (597 ± 156 ml vs.462 ± 220 ml, p = 0.019) and cohort #2 (525 ± 157 ml vs.259 ± 151 ml, p < 0.01). Warters grading scale for mask ventilation was 0.6 ± 1.4 in cohort #1, and 2.6 ± 1.5 in cohort #2.Conclusion: Patients at risk for difficult facemask ventilation may benefit from nasopharyngeal ventilation to maintain adequate ventilation and oxygenation before endotracheal intubation. This ventilation mode may offer another option for ventilation at induction of anesthesia and during the management of respiratory insufficiency, especially in the setting of “unexpected” ventilation difficulty.