Most forms of barotrauma related to mechanical ventilation are known to occur in both adult and pediatric patients. The pressure-driven transfer of gas from the alveolar compartment to the systemic circulation, a devastating complication of ventilatory support in infants, is not generally recognized as a consequence of ventilatory support in adults. Two young adult patients who received ventilatory support with high levels of positive pressure for pneumonia and the adult respiratory distress syndrome developed massive sub-pleural air cysts, interstitial emphysema, and tension pneumothoraces. Despite receiving appropriate treatment for these problems, the patients had recurrent episodes of cerebral infarction, myocardial injury, and a characteristic pattern of livedo reticularis. This distinctive triad of findings, otherwise unexplained and occurring in the setting of cystic barotrauma, is highly suggestive of systemic gas embolism. Although our patients presented with dramatic clinical features, we believe that patients with ventilator-related gas embolism may present more commonly with subtler signs, such as puzzling disturbances in heart rhythm or mental status, seizure activity, hypotension, localized pain, or other embolic manifestations readily ascribed to other causes in critically ill patients.