It has been suggested that compared with other brain tissues, the hippocampus in particular is vulnerable to chronic hypoperfusion. We investigated whether total parenchymal cerebral blood flow (pCBF) was associated with hippocampal atrophy, and also whether this relationship was modified by white matter lesions (WMLs). In a cross-sectional analysis within the SMART-MR (Second Manifestations of ARTerial disease-magnetic resonance) study, which is a cohort study among patients with arterial disease, total CBF (tCBF) and hippocampal volume were assessed in 392 patients (mean age: 62+/-9 years, 84% men). Total CBF was expressed in per 100 mL brain volume for obtaining pCBF. Manual volumetric measurements of the hippocampus were carried out on a three-dimensional fast field-echo T1-weighted magnetic resonance imaging scan with isotropic voxels. Automated brain segmentation was used to quantify volumes of the WML and the total brain. A linear regression analysis showed that reduced pCBF was not associated with smaller hippocampal volume after adjustments were made for age and sex. The association attenuated further after additional adjustments were made for vascular risk factors, lacunar infarcts, and WMLs (beta=0.01 mL per s.d. decrease in pCBF; 95% confidence interval: -0.06 to 0.08). The association was not modified by WML (P-value for interaction term pCBF*WML=0.84). We found no evidence of the fact that lower parenchymal blood flow contributes to the neurodegeneration of the hippocampus in a population of patients with arterial disease.