Abstract Objective: To compare the effect of high-frequency ventilation versus other ventilation methods applied during cardiopulmonary bypass on postbypass oxygenation. Design: Prospective, randomized study. Setting: University hospital. Participants: Seventy-five patients undergoing coronary artery bypass graft surgery. Interventions: Patients were allocated to 5 equal groups of different ventilation methods during bypass. Groups 1 and 2 received high-frequency, low-volume ventilation with 100% and 21% oxygen, respectively. Groups 3 and 4 received 5 cm H2O of continuous positive airway pressure (CPAP) with either 100% or 21% oxygen. Patients from group 5 were disconnected from the ventilator during the bypass period. Measurements and Main Results: Spirometry data, blood gas analysis, oxygen saturation as measured by pulse oximetry, and end-tidal carbon dioxide were recorded 5 minutes before chest opening, 5 minutes before bypass, 5 minutes after bypass, 5 minutes after chest closure and 6, 12, 18, and 24 hours after surgery. There were no differences in compliance and mean airway pressures. Alveolar-to-arterial oxygen gradients increased, and PaO2 decreased significantly (p < 0.05) in all groups 5 minutes after bypass and this trend continued in the postoperative period. Patients from group 3 had higher PaO2 and lower alveolar-to-arterial oxygen gradients, 5 minutes after weaning from bypass (p < 0.05). Extubation times were similar in all groups. Conclusions: The alveolar-arterial oxygen gradient was lower, and the PaO2 was higher 5 minutes after bypass in patients receiving CPAP (100% O2) as compared with those ventilated with high-frequency ventilation. Copyright 2003, Elsevier Science (USA). All rights reserved.