Background Small spotty calcifications in the coronary arteries are associated with an increased risk of myocardial infarction. We examined the association between spotty calcifications near the carotid bifurcations and ipsilateral ischemic stroke in patients with <50% luminal stenosis of the extracranial carotid arteries. Methods and Results We used data from the CAESAR (Cornell Acute Stroke Academic Registry), a prospective registry of all patients with acute ischemic stroke admitted to our institution. We included patients who met criteria for cryptogenic stroke and underwent computed tomography angiography and brain magnetic resonance imaging. Patients with extracranial carotid artery stenosis ≥50% and patients with posterior or bilateral anterior circulation infarcts were excluded. We examined the carotid bifurcations for spotty calcifications, defined as ≥1 contiguous regions of luminal calcification ≤3 mm along the long axis of the vessel. We also measured low-density plaque and maximum plaque thickness. The eligible cohort consisted of 117 patients with a mean age of 66.7±1.65 years with a median National Institute of Health Stroke Scale stroke at the time of arrival of 6 (range, 3-13). The number of spotty calcifications present within a low-density plaque was significantly associated with ipsilateral infarction (0.3±0.8 versus 0.1±0.4, =0.02). Maximum plaque thickness was also significantly associated with ipsilateral infarction (1.4 mm ±1.5 versus 1.0 mm ±1.1, =0.004). Conclusions Spotty calcifications associated with low-density plaque and maximum plaque thickness were associated with ipsilateral ischemic stroke in patients with nonstenotic carotid atherosclerosis, suggesting a role as imaging markers of high-risk plaque.