BACKGROUND: Compartment syndrome occurs when an increase in pressure results in vascular and functional impairment of the underlying nerve and muscles. Thigh compartment syndrome (TCS) is uncommon, but clinical suspicion warrants emergent surgical consultation and fasciotomy. CASE REPORT: We present a 42-year-old man evaluated for right lateral thigh pain, without a history of trauma, deep venous thrombosis (DVT), previous surgery, or intravenous drug use. He was febrile, tachycardic, with a mild leukocytosis, an elevated C-reactive protein level, and an elevated creatinine kinase level. Radiographs showed no abnormality and right lower extremity duplex ultrasound showed no DVT. A computed tomography scan of the right lower extremity was concerning for compartment syndrome. Surgical consultation was obtained, and the patient was taken to the operating room for fasciotomy. He was diagnosed with compartment syndrome intraoperatively. The patient was discharged on hospital day 10. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: TCS is exceedingly rare, especially in the absence of underlying traumatic and nontraumatic etiologies. The diagnosis is challenging because more elastic fascia with larger space in the thigh allows for accommodation of acute increases in pressure. Consequently, there may not be the expected acute rise in compartment pressures; increased compartment pressure may only be a late sign, when underlying neurovascular damage has already occurred. TCS is complicated by high morbidity and mortality. Emergent surgical consultation should be obtained when there is a high clinical suspicion for TCS, and limb-saving fasciotomy should not be delayed. This case shows the importance of a high level of suspicion for TCS in patients with no identifiable etiology and no historical risk factors for development of compartment syndrome, because TCS may not present with classic symptoms.