Introducing mathematically derived variability (MVV) into the otherwise monotonous conventional mechanical ventilation has been suggested to improve lung recruitment and gas exchange. Although the application of a ventilation pattern based on variations in physiological breathing (PVV) is beneficial for healthy lungs, its value in the presence of acute respiratory distress syndrome (ARDS) has not been characterized. We therefore aimed at comparing conventional pressure-controlled ventilation with (PCS) or without regular sighs (PCV) to MVV and PVV at two levels of positive end-expiratory pressure (PEEP) in a model of severe ARDS.