Even a slight increase in pulmonary vascular resistance can overload a normal right ventricle, which ejects blood through a low-pressure circuit. In a clinical setting, a persistent increase in pulmonary vascular resistance produces acute cor pulmonale. From an echocardiographic point of view, may be defined as the combination of a paradoxical septal motion, reflecting systolic overload, with right ventricular enlargement, reflecting diastolic overload. In patients with acute respiratory distress syndrome, this complication reflects the severity of the pulmonary disease involving the microvasculature but may also be caused or exacerbated by an aggressive ventilatory strategy. In the past, conventional respiratory support used in acute respiratory distress syndrome to obtain normocapnia was associated with a poor prognosis and a high frequency of acute cor pulmonale, suggesting some relation between the two findings. This prognosis has greatly improved with protective ventilation. At the same time, the incidence of acute cor pulmonale has diminished in acute respiratory distress syndrome, and the prognosis of this specific complication has also improved, suggesting that the right ventricle may develop some adaptation against persistent overload. Past lessons, however, have taught us that this potential may be limited and lead us to recommend right ventricular protection during mechanical ventilation.