The hyperdense sign is a marker of thrombus in non-contrast computed tomography (NCCT) datasets. The aim of this work was to determine optimal Hounsfield unit (HU) thresholds for thrombus segmentation in thin-slice non-contrast CT (NCCT) and use these thresholds to generate 3D thrombus models. Patients with thin-slice baseline NCCT (≤2.5 mm) and MCA-M1 occlusions were included. CTA was registered to NCCT, and three regions of interest (ROIs) were placed in the NCCT, including: the thrombus, contralateral brain tissue, and contralateral patent MCA-M1 artery. Optimal HU thresholds differentiating the thrombus from non-thrombus tissue voxels were calculated using receiver operating characteristic analysis. Linear regression analysis was used to predict the optimal HU threshold for discriminating the clot only based on the average contralateral vessel HU or contralateral parenchyma HU. Three-dimensional models from 70 participants using standard (45 HU) and patient-specific thresholds were generated and compared to CTA clot characteristics. The optimal HU threshold discriminating thrombus in NCCT from other structures varied with a median of 51 (IQR: 49–55). Experts chose 3D models derived using patient-specific HU models as corresponding better to the thrombus seen in CTA in 83.8% (31/37) of cases. Patient-specific HU thresholds for segmenting the thrombus in NCCT can be derived using normal parenchyma. Thrombus segmentation using patient-specific HU thresholds is superior to conventional 45 HU thresholds.