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Background: A key limitation of conventional ultrasound (US) includes poor differentiation of benign from malignant thyroid nodules. Contrast-enhanced US (CEUS) and acoustic radiation force impulse (ARFI) could provide better characterization of focal thyroid nodules; however, no studies have compared their efficacies. Objective: To evaluate the diagnostic efficacy of conventional US,CEUS, ARFI, and their combined use in differentiating focal solid thyroid nodules. Methods: One-hundred-forty-six Chinese patients with 175 thyroid nodules (119 benign and 56 malignant) were prospectively enrolled. Each patients underwent conventional US, CEUS and ARFI, respectively. The diagnostic performance of the conventional US, CEUS, ARFI, combined use of either CEUS or ARFI and combined use of the three modalities were assessed and compared using Pathological diagnosis (histological/cytological) as the reference method. Results: There were no significant differences between individual groups (CEUS vs US, P = 0.279, ARFI vs US, P = 0.372, CEUS vs ARFI, P = 0.849), combined use of US and CEUS or combined use of US and ARFI yielded significant difference compared to US. (combination of US & CEUS vs US, P = 0.021; combination of US & ARFI vs US, P = 0.036). The combination of three modalities significantly improved the diagnostic accuracy compared with either combination of conventional US and CEUS or combination of conventional US and ARFI (P = 0.045 and P  = 0.027, respectively). Conclusions: CEUS and ARFI can be used as an additional tool in the diagnostic work up of thyroid nodules. The combination of CEUS with ARFI can significantly improve the diagnostic accuracy. [ABSTRACT FROM AUTHOR]