We previously demonstrated a strong relation between carotid atherosclerosis (defined as carotid artery stenosis ≥50%) and intracranial artery calcification (IAC) in ischemic stroke patients. The purpose of this study was to evaluate the relation between aortic atherosclerosis and IAC. Four hundred fifty-four patients with ischemic stroke were included. Complex aortic plaques (CAP) were assessed by transesophageal echocardiography (TEE) and defined as plaques ≥4 mm thick or with mobile components in the proximal aorta. IAC were assessed in the seven major cerebral arteries and a semiquantitative score system was applied, ranging from 0 (no calcification) to 7. Forty-two patients (9.3%) had CAP. Patients with CAP were older compared with patients without CAP (73.6 vs. 63.6 years, p < 0.001), had more vascular risk factors, more significant carotid artery atherosclerosis (p < 0.001), more chronic kidney disease (p < 0.001), and a higher IAC score (3.0 vs. 1.8; p < 0.001). Stepwise logistic regression selected the following independent factors for CAP: previous stroke or TIA (OR 3.3; 95%CI 1.5–7.0; p = 0.002), carotid artery stenosis ≥50% (OR 3.7; 95%CI 1.7–8.0; p = 0.001), chronic kidney disease (OR 3.8; 95%CI 1.9–7.8; p < 0.001), and IAC score (OR 1.5; 95%CI 1.2–1.9; p = 0.002). IAC was present in 100% of patients with CAP. Moreover, IAC had a high sensitivity (100%) and negative predictive value (100%) for the presence of CAP. In ischemic stroke patients, the absence of IAC strongly points to the lack of CAP. However, these results warrant confirmation in prospective studies before concluding the non-utility of the use of TEE to exclude CAP as a potential source of cerebral embolism in patients without IAC.