A 49-year-old man with a history of prostate cancer metastatic to bone suffered a pathological fracture to the left femur while hospitalized (Figure 1A). Eighteen hours after the fracture, he developed hypoxemia and hypotension followed by confusion and a petechial rash in the left axilla. Chest X-ray obtained after intubation demonstrated new diffuse bilateral patchy infiltrates (Figure 1B). Urgent transthoracic echocardiogram showed right ventricular dilation and free wall hypokinesis with preserved contractility of the right ventricular apex (McConnell’s Sign; Figure 2, Movie I in the online-only Data Supplement). Based on the clinical presentation and supportive imaging, the patient was diagnosed with fat embolism syndrome. He was transferred to the intensive care unit for further management. Figure 1. Initial imaging. X-ray of the left lower extremity demonstrating a closed, oblique fracture of the left femur with displacement of the distal femoral fragment ( A ). Chest X-ray obtained shortly after endotracheal intubation showing bilateral patchy infiltrates consistent with acute respiratory distress syndrome (ARDS; B ). Figure 2. Transthoracic echocardiogram images obtained during diastole ( A ) and systole ( B ) demonstrating right ventricular dysfunction with hypokinesis of the mid right ventricular free wall and preservation of the apex. Although it was observed centuries ago that intravenous injection of oil resulted in mechanical obstruction of small vessels,1 the exact pathophysiology of fat embolism syndrome (FES) remains uncertain. Fat embolism (FE) is defined by the presence of fat globules in the pulmonary microcirculation regardless of clinical significance. FES describes a characteristic pattern of clinical findings that follow an insult associated with the release of fat into the circulation. FES is most commonly associated with orthopedic trauma, with highest incidence in closed, long bone fractures of the lower extremities, particularly the femur.2 The risk of FES complicating orthopedic trauma is highest in ages 10 to 40 years and occurs in …