This prospective, single centre, randomised, cross-over study compares patient tolerance of the facemask and mouthpiece for delivery of non-invasive ventilation in an intensive care unit. Twenty-seven patients with acute respiratory failure were scheduled for two 45-min sessions of non-invasive ventilation with facemask and mouthpiece. The order of the sessions was chosen at random. Nurses and patients assessed the tolerance of both techniques using a visual analogue scale. The time spent by nurses and the changes in respiratory parameters were recorded. The facemask was better tolerated than the mouthpiece; all the cases of non-invasive ventilation withdrawal (n = 5) occurred with mouthpieces (p = 0.026). Less nursing time was required using the facemask for the 22 patients who underwent both procedures (p = 0.01). However, the difference in tolerance scores was not significant. Non-invasive ventilation with both facemask and mouthpiece improved the P(a)o(2)/F(i)o(2) ratio, increased the pH and decreased the P(a)co(2). Only non-invasive ventilation with the facemask lowered the respiratory rate. The facemask appears to be a better initial choice for non-invasive ventilation when compared to mouthpiece, but both can be effective.