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Purpose: The purpose of this study is to investigate the diagnostic role of Hounsfield unit (HU) values on noncontrast computed tomography (CT) for differentiating benignity from malignancy in the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) 4-5 nodules with coarse calcifications. Patients and Methods: CT images of 216 ACR TI-RADS 4-5 nodules with coarse calcifications from 207 patients who underwent surgery in our hospital between 2017 and 2019 were retrospectively reviewed. The average HU values (AHUVs) and maximum HU values (MHUVs) of the nodules were measured on noncontrast CT. The distribution of AHUVs and MHUVs in benign and malignant nodules with coarse calcifications was analyzed using the Mann–Whitney test. Receiver operating characteristic (ROC) curves were used to identify the best cut-off values. Diagnostic performances were assessed according to the area under the ROC curve (AUC), sensitivity and specificity. Results: Of the 216 ACR TI-RADS 4-5 nodules with coarse calcifications, 170 were benign and 46 were malignant. The AHUVs of benign and malignant nodules were 791 HU [interquartile range (IQR), 543– 1025 HU] and 486 HU (IQR, 406– 670 HU), respectively (P < 0.001). The MHUVs of benign and malignant nodules were 1084 HU (IQR, 717– 1477 HU) and 677 HU (IQR, 441– 986 HU), respectively (P < 0.001). The AUCs for AHUVs and MHUVs for predicting benign nodules with coarse calcifications were 0.759 and 0.732, and the cut-off values were 627.5 HU and 806.0 HU, with sensitivities of 67.6% and 68.8% and specificities of 73.9% and 67.4%, respectively. The sensitivity and specificity of the combination were 68.8% and 76.1%. Conclusion: AHUVs and MHUVs were helpful in differentiating benignity from malignancy in ACR TI-RADS 4-5 nodules with coarse calcifications. This may provide an important basis for reducing misdiagnosis and unnecessary aspiration or surgical trauma. [ABSTRACT FROM AUTHOR]