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Maintenance of airway patency and oxygenation are the main objectives of face-mask ventilation. Because the incidence of difficult mask ventilation (DMV) and the factors associated with it are not well known, we undertook this prospective study.Difficult mask ventilation was defined as the inability of an unassisted anesthesiologist to maintain the measured oxygen saturation as measured by pulse oximetry > 92% or to prevent or reverse signs of inadequate ventilation during positive-pressure mask ventilation under general anesthesia. A univariate analysis was performed to identify potential factors predicting DMV, followed by a multivariate analysis, and odds ratio and 95% confidence interval were calculated.A total of 1,502 patients were prospectively included. DMV was reported in 75 patients (5%; 95% confidence interval, 3.9–6.1%), with one case of impossible ventilation. DMV was anticipated by the anesthesiologist in only 13 patients (17% of the DMV cases). Body mass index, age, macroglossia, beard, lack of teeth, history of snoring, increased Mallampati grade, and lower thyromental distance were identified in the univariate analysis as potential DMV risk factors. Using a multivariate analysis, five criteria were recognized as independent factors for a DMV (age older than 55 yr, body mass index > 26 kg/m2, beard, lack of teeth, history of snoring), the presence of two indicating high likelihood of DMV (sensitivity, 0.72; specificity, 0.73).In a general adult population, DMV was reported in 5% of the patients. A simple DMV risk score was established. Being able to more accurately predict DMV may improve the safety of airway management.