BACKGROUND Advances in knowledge regarding mechanical ventilation (MV), in particular lung-protective ventilation strategies, have been shown to reduce mortality. However, the translation of these advances in knowledge into better therapeutic performance in real-life clinical settings continues to lag. High-fidelity simulation with a mannequin allows students to interact in lifelike situations; this may be a valuable addition to traditional didactic teaching. The purpose of this study is to compare computer-based and mannequin-based approaches for training residents on MV. METHODS This prospective randomized single-blind trial involved 50 residents. All participants attended the same didactic lecture on respiratory pathophysiology and were subsequently randomized into two groups: the mannequin group (n = 25) and the computer screen-based simulator group (n = 25). One week later, each underwent a training assessment using five different scenarios of acute respiratory failure of different etiologies. Later, both groups underwent further testing of patient management, using in situ high-fidelity simulation of a patient with acute respiratory distress syndrome. RESULTS Baseline knowledge was not significantly different between the two groups (P = 0.72). Regarding the training assessment, no significant differences were detected between the groups. In the final assessment, the scores of only the mannequin group significantly improved between the training and final session in terms of either global rating score [3.0 (2.5-4.0) vs. 2.0 (2.0-3.0), P = 0.005] or percentage of key score (82% vs. 71%, P = 0.001). CONCLUSIONS Mannequin-based simulation has the potential to improve skills in managing MV.