Most of the evidence for HFOV has been from small observational studies,9,19,103,104 often in the setting of refractory hypoxemia. These studies have shown that HFOV is safe and effective, resulting in improvements in oxygenation and providing ample ventilation in adult patients with severe ARDS. There have been only two RCTs of HFOV in adult patients with ARDS.32,105 Derdak et al32 randomized 148 patients to receive either HFOV or conventional ventilation. The HFOV group showed an early improvement in the PaO2/FIO2 ratio, but this was not sustained beyond 24 h. There was a nonsignificant trend toward a lower 30-day mortality in the HFOV group (37% vs 52%; P = .102). A criticism of this trial is that patients in the conventional ventilation group were ventilated with relatively large tidal volumes, which may have contributed to the high mortality in the control group.93 Bollen et al105 reported no significant difference in mortality between patients randomized to HFOV and those to conventional ventilation. A post hoc analysis, however, suggested that HFOV might improve mortality in patients with a higher oxygenation index. Complications reported with HFOV are relatively infrequent and include barotrauma,19,32,100,104 hemodynamic compromise,9,104 mucus inspissations resulting in endo-tracheal tube occlusion or refractory hypercapnia,31 and increased use of sedation or neuromuscular blocking agents.9,19,32,102,106 In the two RCTs comparing HFOV with conventional ventilation, Derdak et al reported no significant effect of HFOV on hemodynamics, barotrauma, or mucus plugging, and Bollen et al did not report any increased risk of complications with HFOV.