To evaluate whether increased cerebrospinal fluid (CSF) pressure causes alteration of periventricular white matter (WM) microstructure in patients with idiopathic intracranial hypertension (IIH). In a prospective study, patients with refractory chronic headache with and without IIH performed a neuroimaging study including 3T MRI, 3D Phase Contrast MR venography, and diffusion tensor imaging (DTI) of the brain. Whole-brain voxel-wise comparisons of DTI abnormalities of WM were performed using tract-based spatial statistics. A correlation analysis between DTI indices and CSF opening pressure, highest peak, and mean pressure was also performed in patients with IIH. We enrolled 62 consecutive patients with refractory chronic headaches. Thirty-five patients with IIH, and 27 patients without increased intracranial pressure. DTI analysis revealed no fractional anisotropy changes, but decreased mean, axial, and radial diffusivity in body (IIHMD = 0.80 ± 0.04, non-IIHMD = 0.84 ± 0.4, IIHAD = 1.67 ± 0.07, non-IIHAD = 1.74 ± 0.05, IIHRD = 0.38 ± 0.04, non-IIHRD = 0.42 ± 0.05 [mm2/sec × 10-3]) of corpus callosum, and in right superior corona radiata (IIHMD = 0.75 ± 0.04, non-IIHMD = 0.79 ± 0.05, IIHAD = 1.19 ± 0.07, non-IIHAD = 1.28 ± 0.09, IIHRD = 0.59 ± 0.03, non-IIHRD = 0.53 ± 0.03 [mm2/sec × 10-3]) of 35 patients with IIH compared with 27 patients without increased intracranial pressure. DTI indices were negatively correlated with high CSF pressures (P < 0.05). After medical treatment, eight patients showed incremented MD in anterior corona radiata left and right and superior corona radiata right. There is significant DTI alteration in periventricular WM microstructure of patients with IIH suggesting tissue compaction correlated with high CSF pressure. This periventricular WM change may be partially reversible after medical treatment.