Coxsackie virus pericarditis caused cardiac tamponade in a 45-day-old infant with corrected total anomalous pulmonary venous drainage and a hypodynamic left heart. The pathophysiology comprised reduced heart compliance, venous return impairment, acute pulmonary hypertension, and increased airway microvascular permeability. Tracheal edema and external compression caused tracheal lumen narrowing and respiratory failure. Laryngoscopy was difficult because of laryngeal inlet swelling. Endotracheal intubation was accomplished with a 3.0-mm tube. Pericardial cavity evacuation resulted in rapid recovery. A postprocedural chest radiograph revealed tracheal lumen enlargement. Repeated laryngoscopy revealed resolution of upper-airway edema. In infants, large pericardial effusions developing after corrective/palliative heart surgery may cause major airway compromise.