Background To maintain cerebral blood flow (CBF), cerebral blood vessels dilate and contract in response to blood supply through cerebrovascular reactivity (CR). Purpose Cardiovascular (CV) disease is associated with increased stroke risk, but which risk factors specifically impact CR is unknown. Study Type Prospective longitudinal. Subjects Fifty‐three subjects undergoing carotid endarterectomy or stenting. Field Strength/Sequence 3T, 3D pseudo‐continuous arterial spin labeling (PCASL) ASL, and T1 3D fast spoiled gradient echo (FSPGR). Assessment We evaluated group differences in CBF changes for multiple cardiovascular risk factors in patients undergoing carotid revascularization surgery. Statistical Tests PRE (baseline), POST (48‐hour postop), and 6MO (6 months postop) whole‐brain CBF measurements, as 129 CBF maps from 53 subjects were modeled as within‐subject analysis of variance (ANOVA). To identify CV risk factors associated with CBF change, the CBF change from PRE to POST, POST to 6MO, and PRE to 6MO were modeled as multiple linear regression with each CV risk factor as an independent variable. Statistical models were performed controlling for age on a voxel‐by‐voxel basis using SPM8. Significant clusters were reported if familywise error (FWE)‐corrected cluster‐level was P < 0.05, while the voxel‐level significance threshold was set for P < 0.001. Results The entire group showed significant (cluster‐level P < 0.001) CBF increase from PRE to POST, decrease from POST to 6MO, and no significant difference (all voxels with P > 0.001) from PRE to 6MO. Of multiple CV risk factors evaluated, only elevated systolic blood pressure (SBP, P = 0.001), chronic renal insufficiency (CRI, P = 0.026), and history of prior stroke (CVA, P < 0.001) predicted lower increases in CBF PRE to POST. Over POST to 6MO, obesity predicted lower (P > 0.001) and cholesterol greater CBF decrease (P > 0.001). Data Conclusion The CV risk factors of higher SBP, CRI, CVA, BMI, and cholesterol may indicate altered CR, and may warrant different stroke risk mitigation and special consideration for CBF change evaluation. Level of Evidence: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:734–747.