To evaluate the diagnostic efficiency of computer-aided diagnosis (CAD) system and 111 radiologists with different experience in identifying benign and malignant thyroid nodules, and to summarize the ultrasound features that may affect the diagnostic of CAD and radiologists.Fifty thyroid nodules and 111 radiologists were enrolled in this study. All the 50 nodules were diagnosed by the 111 radiologists and the CAD system simultaneously. The diagnostic performance of the CAD system, senior and junior radiologists with the maximum accuracy were calculated and compared. Interobserver agreement for different ultrasound characteristics between the CAD and senior radiologist were analyzed.CAD system showed a higher specificity than junior radiologist (87.5% vs 70.4%, P = .03), and a lower sensitivity than the senior radiologist and junior radiologist but the statistics were not significant (76.9% vs 86.9%, P > .5; 76.9% vs 82.6%, P > .5). The CAD system and senior radiologist got larger AUC than junior radiologist but the differences were not statistically significant (0.82 vs 0.76, respectively; P = .5). The interobserver agreement for the US characteristics between the CAD system and senior radiologist were: substantial agreement for hypoechoic and taller than wide (kappa value = 0.66, 0.78), and moderate agreement for irregular margin and micro-calcifications (kappa value = 0.52, 0.42).The CAD system achieved equal diagnostic accuracy to the senior radiologists and higher accuracy than the junior radiologists. The interobserver agreements in the US features between the CAD system and senior radiologist were substantial agreement for hypoechoic and taller than wide; moderate agreement for irregular margin and micro-calcifications. The location of a thyroid nodule and the feature of macrocalcification with wide acoustic shadow may influence the analysis of the CAD system.