Background: Cerebral Fat Embolism (CFE) is a rare though potentially devastating complication of orthopedic injury which can present with neurologic deterioration. Although specific findings have been described, definitive diagnosis of CFE remains challenging. Methods: Retrospective chart review from a major U.S. trauma hospital. Results: Of 33 patients with CFE, all had long bone fractures, 15 had rib fractures, and 16 occurred following orthopedic surgery for long bone fracture. Cutaneous petechiae were documented in 21%. Diagnostic brain MRI was performed in 26 patients. MRI revealed diffusion-restricting lesions in 24 (92%), with 17 (65%) demonstrating the classic “starfield” pattern, and 14 (54%) with hypointense signal on blood sensitive sequences. Transcranial Doppler (TCD) revealed active microemboli in 9 of 17 (53%) cases. Ophthalmologic consultation occurred in 13 with 9 patients found to have retinal hemorrhage or cotton wool spots suggestive of Purtscher or Purtscher-like retinopathy. “Starfield” pattern on MRI was seen in all 9 patients with retinal findings. TCD microemboli were not associated with retinal findings. Conclusions: The optimal diagnostic workup of CFE is complicated by confounding conditions, the unknown sensitivity of diagnostic modalities, and the unclear implications of findings on treatment and outcome. Nonetheless, brain MRI, TCD and ophthalmologic evaluation should be considered in all suspected CFE patients.