Background: Damage of the optic nerve is the major complication of idiopathic intracranial hypertension. A biomarker indicative for optic nerve damage would help identifying high-risk patients requiring surgical procedures. Here, we studied the potential of cerebrospinal fluid neurofilament to predict idiopathic intracranial hypertension-induced optic nerve damage. Methods: In two centers, serum and cerebrospinal fluid of 61 patients with clinically suspected idiopathic intracranial hypertension were prospectively collected. Neurofilament concentrations were measured and related to ophthalmological assessment. Results: The average cerebrospinal fluid neurofilament concentration in patients with moderate and severe papilledema was increased compared to patients with minor and no papilledema (1755 ± 3507 pg/ml vs. 244 ± 102 pg/ml; p < 0.001). Cerebrospinal fluid neurofilament concentrations correlated with the maximal lumbar puncture opening pressure (r = 0.67, p < 0.001). In patients fulfilling the Friedman criteria for idiopathic intracranial hypertension with or without papilledema (n = 35), development of bilateral visual field defects and bilateral atrophy of the optic nerve were associated with increased average age-adjusted cerebrospinal fluid neurofilament concentrations. At last follow-up (n = 30), 8/13 of patients with increased, but only 3/17 with normal, cerebrospinal fluid neurofilament had developed bilateral visual field defects and/or bilateral optic nerve atrophy resulting in a sensitivity of 72.7% and a specificity of 73.7% of cerebrospinal fluid neurofilament to detect permanent optic nerve damage. Conclusions: Cerebrospinal fluid neurofilament is a putative biomarker for optical nerve damage in idiopathic intracranial hypertension.