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Although mechanical ventilation is lifesaving for patients with acute respiratory distress syndrome, it can cause ventilator-induced lung injury. To minimize ventilator-induced lung injury, different ventilatory strategies have been developed. One of the strategies is the use of high-frequency oscillatory ventilation (HFOV).Because of the novel gas exchange mechanisms, HFOV can provide adequate gas exchange using extremely small tidal volumes and maintain high end-expiratory lung volume without inducing overdistension, which should result in minimization of ventilator-induced lung injury.There are convincing clinical and animal data indicating that HFOV is an ideal lung-protective ventilatory strategy, particularly in the setting of neonatal respi-ratory failure, if lung volume recruitment is performed.A recent clinical trial demonstrated early (<16 hrs) improvement in oxygenation with HFOV and a 30-day mortality of 37% with HFOV vs. 52% with pressure-controlled ventilation (p = .102), suggesting that HFOV is as effective and safe as the conventional strategy in adult acute respiratory distress syndrome. Future studies examining optimal algorithms of HFOV using clinically relevant animal models, and patients with acute respiratory distress syndrome, are imperative to determine whether the wide-spread application of HFOV is warranted in adult acute respiratory distress syndrome.