Abstract: Objective To compare the accuracy of two widely used thyroid imaging, reporting and data systems (TI-RADS), namely ACR TI-RADS and Kwak TI-RADS, in the differential diagnosis of benign and malignant thyroid nodules. Methods We reviewed the data of 350 thyroid nodules with definite diagnoses by surgical histopathology (n=144, 41.14%) or fine needle aspiration (FNA) cytopathology (n=206, 58.86%). The nodules were graded using ACR TI-RADS and Kwak TI-RADS based on the ultrasound images, and the diagnostic accuracy of these two systems was evaluated by the area under the receiveroperating characteristic curve (AUC). Results The AUCs of ACR TI-RADS and Kwak TI-RADS were both 0.879. For a differential diagnosis of the thyroid nodules, ACR TI-RADS had a diagnostic sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, Youden’s index and accuracy of 77.3%, 89.1%, 83.0%, 85.1%, 7.101, 0.255, 27.848, 0.664 and 0.843, respectively, with an optimal threshold of TR5, as compared with 84.8%, 84.0%, 78.3%, 89.0%, 5.283, 0.181, 29.265, 0.688 and 0.843, respectively, of Kwak TI-RADS, which had an optimal threshold of 4c. Conclusion Both ACR TI-RADS and Kwak TI-RADS have good performance for differential diagnosis of thyroid nodules, but ACR TI-RADS has a higher specificity and a lower sensitivity compared with Kwak TI-RADS.