Vascular risk factors affect cerebral blood flow ( CBF) and cerebral vascular reactivity, contributing to cognitive decline. Hippocampus is vulnerable to both Alzheimer's disease (AD) pathology and ischemia; nonetheless, the information about the impact of vascular risk on hippocampal perfusion is minimal. Cognitively, healthy elderly (NL = 18, 69.9 ± 6.7 years) and subjects with mild cognitive impairment (MCI = 15, 74.9 ± 8.1 years) were evaluated for the Framingham cardiovascular risk profile ( FCRP). All underwent structural imaging and resting CBF assessment with arterial spin labeling (ASL) at 3T magnetic resonance imaging (MRI). In 24 subjects (NL = 17, MCI = 7), CBF was measured after a carbon dioxide rebreathing challenge. Across all subjects, FCRP negatively correlated with hippocampal (ρ = −0.41, P = 0.049) and global cortical (ρ = −0.46, P = 0.02) vasoreactivity to hypercapnia ( VR_h). The FCRP– VR_h relationships were most pronounced in the MCI group: hippocampus (ρ = 0.77, P = 0.04); global cortex (ρ = 0.83, P = 0.02). The FCRP did not correlate with either volume or resting CBF. The hippocampal VR_h was lower in MCI than in NL subjects ( Z = −2.0, P = 0.047). This difference persisted after age and FCRP correction (F_[3,20] = 4.6, P = 0.05). An elevated risk for vascular pathology is associated with a reduced response to hypercapnia in both hippocampal and cortical tissue. The VR_h is more sensitive to vascular burden than either resting CBF or brain volume.