Sudden cardiac arrest, a rare and often fatal complication of total joint replacement, usually occurs during the insertion of polymethyl methacrylate cement and a prosthesis. We describe a cardiac arrest during insertion of a customized long-stem prosthesis (without the use of a tourniquet) for revision of an earlier total knee replacement. We attribute this complication to the “fat embolism syndrome” (FES)—hypoxemia from an acute pulmonary embolism composed of fat and marrow elements extruded into the venous circulation—coupled with systemic hypotension from absorption of the cement monomer. The syndrome appears to be more common when long-stem prostheses are used. Hypoxemia also correlates with the release of tissue-thromboplastic products as well as the bone marrow elements. Phase 1 of the syndrome consists of particulate obstruction of the pulmonary circulation that causes cor pulmonale and bradycardia or other dysrhythmia. Phase 2 is characterized by respiratory and neurologic manifestations associated with the classic conception of the syndrome. Intraoperative increases in pulmonary artery and pulmonary artery occlusion pressures and pulmonary vascular resistance during unexplained hypoxemia should alert the clinician to the possibility of FES. Proper diagnosis relies on recognizing the three most common clinical manifestations: hypoxemia, neurologic derangements, and fever. Other manifestations of FES are petechiae, thrombocytopenia, anemia, lipuria, changes on ECG, tachycardia, and dyspnea.