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Lung-protective mechanical ventilation is not sex neutral. Ventilator-induced lung injury can be mitigated with a lung-protective ventilation strategy that includes ventilation with low tidal volumes. Mortality in acute respiratory distress syndrome (ARDS) remains higher in females than in males, and females with ARDS are less likely to receive lung-protective ventilation compared with males because of their shorter height and greater error when body height is visually estimated. In addition, lung-protective ventilation might be less effective in females because of differences in respiratory physiology not accounted for by the formula commonly used to assess body weight, and because of several clinically important sex-specific differences in extrapulmonary biology and management of critical illness.