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Background: Differentiating between benign and malignant thyroid nodules requires close attention for clinicians.Ultrasound feature such as irregular margins, microcalcification or intranodular blood flow was believed as malignant indicators.Hashimotos thyroiditis (HT) was also considered as a risk factor of malignant nodules.How should clinicians assess the diagnostic values of these factors? Methods: 3780 patients who had undergone thyroidectomy were included in this retrospective study.Frequencies of different combinations of ultrasound features intranodular blood flow, irregular margins and microcalcification were described.The associations between ultrasound features as well as pathological HT and malignant nodules were analyzed.The appealing receiver operating characteristic (ROC) curve was used to assess the ability of ultrasound features and pathological HT to predict malignancy.Results: 2,708 patients were diagnosed with pathologically benign nodules, whereas 1,072 patients suffered from malignant nodules.The incidence of pathological HT was higher in malignant nodules vs.benign nodules (17.12% vs.7.00%, P < 0.001).The frequency of ultrasound features of isolated irregular margins, microcalcification or intranodular blood flow was not higher in malignant group.Noticeably, the prevalence of intranodular blood flow combined with irregular margins (24.31% vs.7.35%, p<0.001) or with microcalcification (15.21% vs.6.09%, p<0.001) was more frequent in malignant group compared to benign group.The rate of combined three features was significantly higher in malignant nodules (21.18% vs.1.22%, p<0.001).Irregular margins (OR 9.7;95%CI 8.1-11.7), microcalcification (OR 6.1;95%CI 5.0-7.4), intranodular (OR 1.693;95%CI 1.4-2.1) and pathological HT (OR 1.947;95%CI 1.5-2.5) were independently risk facotrs for malignant nodules in a multivariate analysis.Area under curve (AUC) was calculated as 0.82 for the combined three ultrasound features, which reached 0.83 when including pathological HT.Conclusions: Coexistence of irregular margins, microcalcification and intranodular blood flow improves the predictive power of malignant nodules.Pathological HT is identified as a risk factor for malignant nodules though with little additive power to predict malignancy.