There are no existing data regarding risk factors for impossible mask ventilation and limited data regarding its incidence. The authors sought to determine the incidence, predictors, and outcomes associated with impossible mask ventilation. The authors performed an observational study over a 4-yr period. For each adult patient undergoing a general anesthetic, preoperative patient characteristics, detailed airway physical exam, and airway outcome data were collected. The primary outcome was impossible mask ventilation defined as the inability to exchange air during bag-mask ventilation attempts, despite multiple providers, airway adjuvants, or neuromuscular blockade. Secondary outcomes included the final, definitive airway management technique and direct laryngoscopy view. The incidence of impossible mask ventilation was calculated. Independent (P < 0.05) predictors of impossible mask ventilation were identified by performing a logistic regression full model fit. Over a 4-yr period from 2004 to 2008, 53,041 attempts at mask ventilation were recorded. A total of 77 cases of impossible mask ventilation (0.15%) were observed. Neck radiation changes, male sex, sleep apnea, Mallampati III or IV, and presence of beard were identified as independent predictors. The receiver-operating-characteristic area under the curve for this model was 0.80 +/- 0.03. Nineteen impossible mask ventilation patients (25%) also demonstrated difficult intubation, with 15 being intubated successfully. Twelve patients required an alternative intubation technique, including two surgical airways and two patients who were awakened and underwent successful fiberoptic intubation. Impossible mask ventilation is an infrequent airway event that is associated with difficult intubation. Neck radiation changes represent the most significant clinical predictor of impossible mask ventilation in the patient dataset.