BACKGROUND AND PURPOSE: Changes at the optic nerve head on DWI in the presence of papilledema have not been systematically studied. The purpose of this study was to evaluate if hyperintensity of ON heads on DWI is associated with papilledema. MATERIALS AND METHODS: In this retrospective study, 19 patients (4 men, 15 women; median age, 32 years) with papilledema and 20 control participants (7 men, 13 women; median age, 48 years) who had undergone prior MR imaging of the brain were identified. Two neuroradiologists blinded to the diagnosis independently reviewed the DWI for the presence of hyperintense signal at the ON head of each eye. If present, they graded the signal as mild or prominent. Groups with and without papilledema were compared for the prevalence of ON head hyperintensity by using the Fisher exact test, with analyses performed both for groups of patients and for individual eyes. Presence of ON head hyperintensity was also studied as a function of Frisen papilledema grade on fundoscopy, when available. RESULTS: Hyperintensity of the ON heads on DWI was significantly associated with papilledema (P = .001). For the 2 readers, hyperintensity at both ON heads was 26.3% and 42.1% sensitive and 100% specific in the detection of papilledema. The presence of unilateral ON head hyperintensity was not specific for papilledema and was invariably graded as mild when seen in the control group. Patients with higher papilledema grades had a higher prevalence of hyperintensity at the ON heads. CONCLUSIONS: Hyperintensity of the ON heads on DWI can serve as a useful imaging marker for papilledema, especially if bilateral. Its absence, however, does not exclude papilledema.