Qi Zhou,1 Wenjun Wu,1 Fang Wang,2 Xiaohua Gong,1 Xiaojun Chen1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325015, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325015, People’s Republic of ChinaCorrespondence: Xiaohua Gong; Xiaojun ChenDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Ouhai District, Wenzhou, Zhejiang, 325015, People’s Republic of ChinaEmail gxh1204@163.com; chenxiaojun_dr@yeah.netObject: To evaluate the effects of ultrasound-guided fine-needle aspiration with or without negative pressure (FNA+P or FNA-P) on diagnosis of thyroid nodules.Methods: A prospective randomized study was performed. Patients (n=1374, female=1094, 79.6%, male=280, 20.4%, age=48.7± 12.5 yr) with thyroid nodules were randomly divided into FNA-P (n=774, 56.3%) and FNA+P (600, 43.7%) groups. Thyroid nodules were diagnosed by FNA-P or FNA+P, in the left (n=640, 46.6%) and right (n=734, 53.4%).Results: The thyroid nodules were diagnosed as microcalcification (n=751, 54.7%), coarse calcification (n=404, 29.4%), peripheral calcification (n=101, 7.4%) and mixed micro + coarse calcification (n=118, 8.6%). Based on Bethesda classification criteria, the thyroid nodules were cataloged as type I (n=217,15.8%), II (n=467, 34.0%), III (n=151, 11.0%), V (n=333, 24.2%), and VI (n=206, 15.0%). There were no significant differences between experimental groups diagnosed by FNA-P or FNA+P.Conclusion: The results suggest that fine-needle aspiration with or without negative pressure does not significantly affect the sensitivity of thyroid nodule diagnosis.Keywords: thyroid nodules, ultrasound-guided fine-needle aspiration, negative pressure, diagnosis