Objective: To assess the feasibility of time-intensity curve (TIC) analysis of contrast-enhanced ultrasound (CEUS) in demonstrating features of benign and malignant thyroid nodules. Methods: CEUS images of 98 patients with 103 thyroid nodules were retrospectively analyzed. The final diagnosis was confirmed by histology after surgical excision, or cytology after fine needle aspiration (FNA). Among the benign nodules, which were confirmed using cytology and not surgically removed, those with a > 50% cystic component that showed no changes for 1 year on follow-up US, were diagnosed as clinically benign nodules. Similarly, nodules with a < 50% cystic component that were aspirated twice and showed no changes for 1 year on follow-up US were also regarded as clinically benign nodules. TIC parameters, including perfusion parameters of relative values (RV) of peak intensity (PI) (Delta PI), RV of rise time (Delta RT), RV of time to peak (Delta TTP), RV of maximum slope coefficient (MSC) of wash-in (Delta MSCWI), RV of area under the rising curve (Delta AUC(R)), clearance parameters of RV of area under the falling curve (Delta AUC(F)), RV of MSC of washout (Delta MSCWO), comprehensive parameters of RV of mean transit time (Delta MTT), and area under the falling curve (Delta AUC(F)) were observed. Results: Compared with benign thyroid nodules, malignant nodules on TIC analysis of CEUS showed a lower Delta PI (119.73 (115.34, 129.7), -15.82 (-17.7, -4.31)), later Delta RT (-0.27 (-0.51, -0.2), 0.58 (-0.26, 0.65)) and Delta TTP (-0.52 (-0.55, -0.36), 0.69 (-0.04, 0.74)), gentler Delta MSCWI (6.18 (5.29, 7.44), -6.1 (-7.6, 2.14)), and smaller AUC(R) (75.7 (56.95, 93.22), -88.43 (-108.89, -73.21)) in perfusion parameters; a smaller Delta AUC(F) (112.92 (87.77, 137.58), -75.55 (-105.28, -59.32)) in clearance parameters; and a smaller Delta AUC (181.7 (151.50, 219.06), -160.64 (-200.08, -144.11)), and an earlier Delta MTT (2.00(1.85, 3.14), -2.09 (-2.48, -0.95)) in comprehensive parameters (P < 0.05). Multivariate analysis of RV of TIC parameters demonstrated that Delta MSCWI (OR = 0.112; 95% confidence interval [CI], 0.025-0.507) and Delta MTT (OR = 0.099; 95% CI, 0.028-0.346) were protective factors. Conclusions: TIC of CEUS is a very promising and valuable technique for differentiating benign and malignant thyroid nodules.