Abstract Rationale: Fat embolism syndrome (FES) is composed of a triad of symptoms, including respiratory distress, neurologic deficit, and petechiae. Respiratory distress usually presents first before the other symptoms. Thrombotic pulmonary embolism (TPE) is a differential diagnosis of FES. Trauma is a risk factor for both diseases; however, co-occurrence is rare. Patient concerns: A 35-year-old male patient presented with altered consciousness, focal neurologic deficit, and respiratory distress after a left femoral subtrochanteric fracture and subsequent open reduction and internal fixation with an intramedullary nail. Diagnosis: Computed tomography pulmonary angiography (CTPA) revealed lower pulmonary artery filling defects and ground-glass opacities in bilateral lung, indicating TPE and FES, respectively. Interventions: Heparin was initially added and subsequently switched to apixaban. The symptoms improved quickly without major bleeding complications. Lession Subsections: Concomitant TPE and FES after trauma are rare and require different treatment approaches. Due to clinical similarities, prompt chest CTPA was advised to detect TPE that was treated with anticoagulant therapy instead of supportive care for FES.