To investigate the efficiency of contrast-enhanced ultrasound (CEUS) features, particularly ring-enhancement patterns, in the differential diagnosis of thyroid nodules. 302 nodules with CEUS ring-enhancement were retrospectively enrolled, including 135 benign and 167 malignant ones. The ring-enhancement patterns were classified into regular and irregular hyper- or hypo-ring enhancement. Comparative analyses of ultrasound (US) and CEUS features between benign and malignant nodules were performed. The diagnostic performances of the ring-enhancement patterns and Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) were compared in nodules with different sizes. Irregular hypo-ring enhancement was much more common in malignancies than that in benign ones, and it was an independent predictor for thyroid malignant nodules. With irregular hypo-ring enhancement as the diagnostic criteria for malignant nodules, the specificity was higher than that of C-TIRADS (85.2% vs. 75.6%, p = .037) while the AUC was comparable (0.845 vs. 0.803, p = .136) in all nodules. When the nodule size was taken into account, the specificity and AUC were both significantly higher than those of C-TIRADS (92.8% vs. 81.1%, p = .021; 0.907 vs. 0.823, p = .026) in nodules ≥10 mm, which can decrease the unnecessary FNA rate. Irregular hypo-ring enhancement was a valuable CEUS feature for the differential diagnosis of thyroid nodules, especially in nodules ≥10 mm.