An 83-year-old woman was transferred to our cardiac intensive care unit with an acute non-Q-wave myocardial infarction and pulmonary edema. Enoxaparin was one component of the treatment regimen used. Her hospital course was complicated by episodes of hypotension, as well as by recurrent left hip and left thigh pain. The defining event occurred when the patient became acutely hypotensive and developed abdominal distention, peritoneal signs. intense left flank pain, and a 3.3 g/dl hemoglobin decrease. Abdominal computed tomography showed a 9 X 6 X 20 cm left retroperitoneal hematoma. The hematoma was spontaneous, secondary to enoxaparin use. The patient died despite vigorous supportive care, Enoxaparin is being increasingly used in patients with acute coronary syndromes. Review of the medical literature revealed that this is the first reported case of a patient with an acute coronary syndrome who died as a result of an enoxaparin-induced, spontaneous retroperitoneal hematoma. This article reviews important clinical signs and symptoms, identifies high-risk patient populations, and discusses management strategies.