Objective: To investigate the effect of ultrasound by computer aided diagnosis (CAD) system in diagno-sing nodules in patients with diffuse thyroid lesions. Methods: A total of 342 patients with diffuse thyroid lesions and thyroid nodules who underwent thyroid surgery in our hospital during August 2017 to December 2017 were enrolled. Based on guidelines for adult thyroid nodules and differentiated thyroid cancer, ultrasound with and without CAD were performed on 533 nodules from the patients. The findings of ultrasound were compared with pathological results, and sensitivity, specificity, positive predictive value, negative predictive value, and area under the ROC curve(AUC) were calculated to observe difference in efficacy between ultrasound and ultrasound by CAD system. Results: The sensitivity, specificity of conventional ultrasound for diagnosing malignant and benign nodules in diffuse thyroid lesions was 96.6%, 72.5%, with AUC of 0.846. While the diagnostic sensitivity, specificity of ultrasound and ultrasound by CAD system was 96.6%, 80.9%, with AUC of 0.888. The use of CAD system enabled ultrasound achieve a higher specificity and AUC (P<0.01). Conclusions: For patients with diffuse thyroid lesions, ultrasound aided by CAD has a better specificity in diagnosis of thyroid nodules, which may reduce unnecessary puncture biopsies.