A 17-year-old with severe hypertrophic cardiomyopathy (HCM) presented to the emergency department with symptoms of cough, shortness of breath, chest pain, and tactile fevers. She was initially admitted to the cardiac floor, and later transferred to the cardiothoracic intensive care unit on day 5 of illness with deterioration over the next week from BiLevel positive airway pressure to endotracheal intubation. The patient met criteria for severe acute respiratory distress syndrome (ARDS). Standard ARDS lung-protective strategies were refined in consideration of complications caused by her HCM. Such complications included dynamic cardiac outflow obstruction, myocardial ischemia with tachycardia, elevated pulmonary vascular resistance from diastolic dysfunction, and narrow fluid balance window to reduce pulmonary edema while maintaining adequate left ventricular preload. The patient remained refractory despite broad-spectrum antibiotics requiring multiple vasoactive medications, aggressive ventilator management, and inhaled nitric oxide. Social history revealed "vaping" cannabis with butane hash oil prior to symptom onset. Corticosteroids were initiated 2 weeks after initial presentation (day 9 of mechanical ventilation) with rapid recovery and resolution of illness. Acute respiratory distress syndrome is an aggressive disease in the intensive care unit. E-cigarette or vaping product use-associated lung injury is increasingly recognized as a cause of ARDS in adolescents and adults. A complete social history is essential and must be obtained early in all such patients presenting with symptoms of acute respiratory distress and revisited throughout the hospital stay if no other reason for the ARDS is discovered. Disease progression may be subacute with a long interval between onset of symptoms and peak symptoms. The risk of barotrauma is high despite lung-protective ventilation strategies. Management is supportive with resolution over days to weeks. However, other clinical factors may considerably complicate management in cases of underlying comorbidities.