Background Stenosis has historically been the major factor used to determine carotid stroke sources. Recent evidence suggests that specific plaque features detected on imaging may be more highly associated with ischemic stroke than stenosis. We sought to determine computed tomography angiography (CTA) imaging features of carotid plaque that optimally discriminate ipsilateral stroke sources. Methods and Results In this institutional review board-approved retrospective cross-sectional study, 494 ipsilateral carotid CTA-brain magnetic resonance imaging pairs were available for analysis after excluding patients with alternative stroke sources. Carotid CTA and clinical markers were recorded, a multivariable Poisson regression model was fitted, and backward elimination was performed with a 2-sided threshold of <0.10. Discriminatory value was determined using receiver operating characteristic analysis, area under the curve, and bootstrap validation. The final CTA carotid-source stroke prediction model included intraluminal thrombus (prevalence ratio, 2.8 <0.001; 95% CI, 1.6-4.9), maximum soft plaque thickness (prevalence ratio, 1.2 <0.001; 95% CI, 1.1-1.4), and the rim sign (prevalence ratio, 2.0 =0.007; 95% CI, 1.2-3.3). The final discriminatory value (area under the curve=78.3%) was higher than intraluminal thrombus (56.4%, <0.001), maximum soft plaque thickness (76.4%, =0.007), or rim sign alone (69.9%, =0.001). Furthermore, NASCET (North American Symptomatic Carotid Endarterectomy Trial) stenosis categories (cutoffs of 50% and 70%) had lower stroke discrimination (area under the curve=67.4%, <0.001). Conclusions Optimal discrimination of ipsilateral carotid sources of stroke requires information on intraluminal thrombus, maximum soft plaque thickness, and the rim sign. These results argue against the sole use of carotid stenosis to determine stroke sources on CTA, and instead suggest these alternative markers may better diagnose vulnerable carotid plaque and guide treatment decisions.