Sixty-seven patients with ICA/M1 MCA segment thrombus treated with IV alteplase were included in this analysis. Three hundred twenty-six radiomics features were extracted from each thrombus on both NCCT and CTA images. Linear discriminative analysis was applied to select features most strongly associated with early recanalization with IV alteplase. These features were then used to train a linear support vector machine classifier. Thrombus radiomics features derived from NCCT and CTA are more predictive of recanalization with IV alteplase in patients with acute ischemic stroke with proximal occlusion than previously known thrombus imaging features such as length, volume, and permeability. BACKGROUND AND PURPOSE: Thrombus characteristics identified on non-contrast CT (NCCT) are potentially associated with recanalization with intravenous (IV) alteplase in patients with acute ischemic stroke (AIS). Our aim was to determine the best radiomics-based features of thrombus on NCCT and CT angiography associated with recanalization with IV alteplase in AIS patients and proximal intracranial thrombi. MATERIALS AND METHODS: With a nested case-control design, 67 patients with ICA/M1 MCA segment thrombus treated with IV alteplase were included in this analysis. Three hundred twenty-six radiomics features were extracted from each thrombus on both NCCT and CTA images. Linear discriminative analysis was applied to select features most strongly associated with early recanalization with IV alteplase. These features were then used to train a linear support vector machine classifier. Ten times 5-fold cross-validation was used to evaluate the accuracy of the trained classifier and the stability of the selected features. RESULTS: Receiver operating characteristic curves showed that thrombus radiomics features are predictive of early recanalization with IV alteplase. The combination of radiomics features from NCCT, CTA, and radiomics changes is best associated with early recanalization with IV alteplase (area under the curve = 0.85) and was significantly better than any single feature such as thrombus length (P < .001), volume (P < .001), and permeability as measured by mean attenuation increase (P < .001), maximum attenuation in CTA (P < .001), maximum attenuation increase (P < .001), and assessment of residual flow grade (P < .001). CONCLUSIONS: Thrombus radiomics features derived from NCCT and CTA are more predictive of recanalization with IV alteplase in patients with acute ischemic stroke with proximal occlusion than previously known thrombus imaging features such as length, volume, and permeability.