Abstract: Objective To study the role of contrast-enhanced ultrasonography in differential diagnosis of benign and malignant thyroid nodules. Methods Sixty patients with 95 thyriod nodules admitted to our hospital from December 2012 and May 2013 for routine ultrasonography and contrast-enhanced ultrasonography were included in this study. Distribution of blood perfusion in their thyroid nodules was observed. Time-intensity curves for benign and malignant thyroid nodules were analyzed and compared with those for pathologically-diagnosed benign and malignant thyroid nodules. Results Contrast-enhanced ultrasonography showed that the benign thyroid nodules were mainly manifested as ring enhancement(30/40) and hypo-enhancement(29/40) and malignant thyroid nodules were mainly manifested as inhomogeneous enhancement(50/55) and low enhancement(38/55). The peak time was shorter in malignant nodules than in benign nodules. The sharpness of and area under the curve were higher in malignant nodules than in benign nodules. Thyriod nodules puncture and postoperative pathology revealed that 40 were benign nodules and 55 were malignant nodules. The sensitivity, specificity and accuracy of routine ultrasonography were 78.2%, 82.5% and 80% respectively and those of contrast-enhanced ultrasonography were 94.5%, 95% and 94.5% respectively. Conclusion Contrast-enhanced ultrasonography can provide valuable qualitative and quantitative evidence for the differential diagnosis of benign and malignant thyroid nodules.