Introduction Duplex ultrasound (DUS) velocity measurement is the preferred method for evaluating carotid artery stenosis. However, velocity criteria based upon native carotid arteries may not apply to internal carotid artery stents. Previously, catheter-based angiography was used to determine DUS velocity criteria for in-stent restenosis (ISR), but conventional angiography is invasive and can be limited. This study sought to define duplex ultrasound velocity criteria for predicting internal carotid artery in-stent restenosis by correlating in-stent velocities with computed tomographic angiography (CTA) measurements of percent stenosis. Methods A retrospective chart review was conducted on all patients who underwent internal carotid artery (ICA) stenting within our health system between January 2013 and February 2020. Thirty-eight surveillance DUS studies from 32 patients were found to have CTA performed within 30 days. Centerline reconstructions of internal carotid artery stents were created using Aquarius iNtuition software (TeraRecon, Durham, NC, USA). Two independent observers measured percent stenosis by three built-in methods. Stenotic areas were matched to DUS-measured peak systolic velocities (PSV) and end-diastolic velocities (EDV). Internal carotid artery PSV (stent) to common carotid artery (CCA) PSV ratios (ICA/CCA) were calculated, and receiver operating characteristic (ROC) curves were generated. The optimal DUS velocity criteria in the stented ICA were determined by maximizing Youden's index. Results Mean vessel diameter measurement of percent stenosis resulted in the most accurate model for all DUS velocity parameters (PSV, EDV, and ICA/CCA ratio) and was used for threshold determinations (area under the receiver operating characteristics (AUROC): 0.99, 0.96, and 0.96, respectively). A PSV cutoff of 240 cm/s for ≥60% ISR resulted in the highest Youden's index (97%) with 100% sensitivity and 97% specificity. Secondary DUS parameters included an EDV ≥50 cm/s (Youden's index 84%) and an ICA/CCA ratio ≥ 2.2 (Youden's index 91%). Conclusions Velocity criteria to predict internal carotid artery ISR is needed to inform decisions for possible reintervention. Using CTA, we found that a PSV ≥240 cm/s on carotid DUS can predict ≥60% ISR with high sensitivity and specificity. This value can be used as an alternative to current velocity criteria based on native carotid arteries. However, the optimal thresholds for EDV and ICA/CCA ratio were similar to native carotid arteries.