A 22-year-old Asian woman presented with respiratory distress, cough, and wheezing for 1 week. Prior history included asthma and Turner syndrome. On presentation to the emergency department, the patient was hypotensive, tachycardic, tachypneic, with an oxyhemoglobin saturation in the mid 80% range while breathing ambient air. Chest radiograph revealed pulmonary vascular congestion and a left lower lobe infiltrate. Endotracheal intubation, mechanical ventilation, and vasopressors were initiated. Empiric therapy for community-acquired pneumonia was administered utilizing broad-spectrum intravenous antibiotics. Routine sputum culture was negative for pathogens. Nasopharyngeal swab submitted for multiplex amplified nucleic acid testing yielded enterovirus-human rhinovirus (EV-HRV). Thus, the diagnosis of EV-HRV pneumonia complicated by acute respiratory distress syndrome (ARDS) was established. Multiple attempts to wean from the ventilator were unsuccessful, and a tracheostomy was performed. This report highlights EV-HRV as a cause of severe ARDS and prolonged respiratory failure in adults.