<h3>Objective:</h3> To report the <b><i>clinical</i></b> experience of resting state fMRI (rs-fMRI) for neuroprognostication, consciousness recovery, and epileptogenic networks in acute coma. <h3>Background:</h3> Diagnosis and prognosis in acute disorders of consciousness (DoC) remains a challenge. Early withdrawal of care for traumatic brain injury (TBI) patients with recovery potential and continuation of care for patients with devastating prognosis due to misdiagnosis of DoC have both been reported. The rs-fMRI is an innovative tool that has shown promise in diagnosis and prognosis of DoC but has yet to see widespread clinical use. <h3>Design/Methods:</h3> Case Report. <h3>Results:</h3> We present a case of a previously healthy 38-year-old man who received clinical rs-fMRI in acute coma due to TBI. Initial exam: nonreactive pupils, intact corneal reflexes, absent cough and gag reflexes and no motor response. His Glasgow Coma Scale (GCS) was 3 and Coma Recovery Scale-Revised (CSR-R) score was 0. CT head showed acute left subdural hematoma, rightward midline shift, and uncal herniation. After undergoing emergent hemicraniectomy, MRI brain showed evolving Grade III diffuse axonal injury, severe ventriculomegaly, and protrusion of cortex through the hemicraniectomy. EEG demonstrated bilateral slowing but no seizures. Rs-fMRI (hospital day 36) demonstrated no epileptogenic networks, preserved default mode network, language and subcortical motor networks with moderate impairment. These findings supported return of consciousness, lower-level language comprehension, and motor impairment. Despite the patient’s poor initial examination, the rs-fMRI was useful in supporting the family’s decision to continue care. At three months, the patient’s CSR-R improved to 9, including regained localization to sound, visual fixation, flexion withdrawal, oral reflexive movements, no communication, and eye opening without stimulation, which is consistent with minimally conscious state minus. <h3>Conclusions:</h3> Clinical utilization of rs-fMRI has limitations but can aid in clinical decision-making when evaluating for epileptogenic networks, potential for consciousness recovery, and overall functional outcome in patients with DoC and severe TBI. <b>Disclosure:</b> Dr. Aseem has nothing to disclose. Dr. Strohm has nothing to disclose. Dr. Carlson has nothing to disclose. Dr. Karazanashvili has nothing to disclose. Dr. Gilbert has nothing to disclose. Ms. Gillette has nothing to disclose. Dr. Boerwinkle has nothing to disclose.