A 58-year-old woman with chronic obstructive pulmonary disease had spontaneous bilateral hemothorax and a retroperitoneal hematoma after 4 days of anticoagulation therapy with enoxaparin (1 mg/kg subcutaneously every 12 hours) for suspected pulmonary thromboembolism. The patient was successfully managed with red blood cell and plasma transfusions, multiple thoracenteses for evacuation of blood from the pleural space, short-term mechanical ventilation, and administration of bronchodilators, corticosteroids, and antibiotics. This is the first report of spontaneous hemothorax and the third report of spontaneous retroperitoneal hematoma associated with enoxaparin therapy.