Regional brain perfusion is supplied by flow from subcortical conduit vessels, namely the anterior, middle and cerebral arteries, and the functionality of these vessels is largely characterized by vasoreactivity to physiological stimuli. Patients with cardiovascular disease, such as ischemic heart disease (IHD), are at greater risk for stroke, a risk determined in part by cerebrovasoreactivity tests (i.e., dilation or constriction). Patients with osteoarthritis (OA) express greater incidence of cardiovascular disease. However, whether these patients express impaired cerebrovascular reactivity, and how such changes are manifest in each subcortical conduit vessel, remain unanswered. This study tested the hypothesis that, compared to healthy individuals (CTL), those either IHD or OA exhibit heterogeneous yet impaired reactivity (change in cross‐sectional area, ΔCSA) in the basilar and all Circle of Willis conduit in response to elevated levels of end‐tidal CO 2 (ETCO 2 ). In 22 participants (CTL: 6, OA: 7, IHD: 9; age range: 40–75 years), we collected simultaneous subcortical vascular responses (i.e., vasoreactivity) during normocapnia and hypercapnia (gas mixture of 5% CO 2 , 95% oxygen; ADInstruments Powerlab) conditions using a 3 Tesla Siemens MAGNETOM Fit scanner and T1‐weighted pulse sequence (0.7 mm isotropic). The relative change in cross‐sectional area (%ΔCSA) in response to CO 2 , measured at a site perpendicular to the direction of flow, of the basilar, left and right internal carotid, anterior, middle, and posterior cerebral arteries (9 vessels total) were measured using OsiriX software. The cross‐sectional vasoreactivity to changes in ETCO 2 (ΔETCO 2 ) was calculated as %ΔCSA/ΔETCO 2 . In all 9 vessels, OA and IHD patients exhibited similar vasoreactivity; yet, relative to CTL, OA and IHD patients had lower reactivity (%/mm Hg; mean ± S.D.) in the right anterior cerebral (CTL: 16.3 ± 6.5, OA: 3.8 ± 4.1, IHD: 4.4 ± 9.4; p<0.05), right internal carotid (CTL: 8.9 ± 4.9, OA: 3.9 ± 2.9, IHD: 1.5 ± 1.5; p<0.05), and basilar arteries (CTL: 7.8 ± 4.6, OA: 0.7 ± 0.8, IHD: 2.9 ± 3.0; p<0.05). Additionally, relative to CTL, OA patients expressed less left anterior cerebral artery reactivity (CTL: 11.6 ± 6.5, OA: 2.3 ± 1.2, IHD: 3.5 ± 8.3; p<0.05), and IHD patients had diminished right middle cerebral artery reactivity (CTL: 22.4 ± 17.4, OA: 5.6 ± 6.4, IHD: 3.7 ± 4.8; p<0.05). Therefore, heterogeneous patterns of dilation across subcortical vessels was observed in all groups, but the patient groups exhibited significantly impaired vasoreactivity in many of these vessels compared to healthy individuals. Support or Funding Information Supported by The University of Western Ontario Bone and Joint Institute Catalyst grant and the Canadian Institute of Health Research grant (201503MOP‐342412‐MOV‐CEEA).