We compared implementation of systematic airway assessment with existing practice of airway assessment on prediction of difficult mask ventilation. Twenty-six departments were cluster-randomised to assess eleven risk factors for difficult airway management (intervention) or to continue with their existing airway assessment (control). In both groups, patients predicted as a difficult mask ventilation and/or difficult intubation were registered in the Danish Anaesthesia Database, with a notational summary of airway management. The trial's primary outcome was the respective incidence of unpredicted difficult and easy mask ventilation in the two groups. Among 94,006 patients undergoing mask ventilation, the incidence of unpredicted difficult mask ventilation in the intervention group was 0.91% and 0.88% in the control group; (OR) 0.98 (95% CI 0.66-1.44), p = 0.90. The incidence of patients predicted difficult to mask ventilate, but in fact found to be easy ('falsely predicted difficult') was 0.64% vs. 0.35% (intervention vs. control); OR 1.56 (1.01-2.42), p = 0.045. In the intervention group, 86.3% of all difficult mask ventilations were not predicted, compared with a higher proportion 91.2% in the control group, OR 0.61 (0.41-0.91), p = 0.016. The systematic intervention did not alter the overall incidence of unpredicted difficult mask ventilations, but of the patients who were found to be difficult to mask ventilate, the proportion predicted was higher in the intervention group than in the control group. However, this was at a 'cost' of increasing the number of mask ventilations falsely predicted to be difficult.