To evaluate the safety and efficacy of US-guided microwave ablation in patients with thyroid nodules at Zuckerkandl tubercle.103 consecutive patients with thyroid nodules at Zuckerkandl tubercle (ZTTN) were enrolled in this study from November 2017 to August 2021. Prior to the surgery or US-guided microwave ablation (MWA), preoperative ultrasound visualization of the recurrent laryngeal nerve (RLN) and ZTTN was performed, the size and the position relationship between them were observed. Patients were followed up at 1, 3, 6, and 12 months after MWA and the volume reduction rates (VRR) of the thyroid nodules were analyzed.All patients successfully had the RLN and ZTTN detected using ultrasound before surgery or ablation with a detection rate of 100%. For the 103 patients, the majority of ZTTN grades were categorized as grade 2, with the distance from the farthest outside of ZTTN to the outer edge of thyroid ranging between 6.0 and 10.0 mm. The position relationship between ZTTN and RLN was predominantly type A in 98 cases, with type D observed in 5 cases. After MWA, the median nodule volume had significantly decreased from 4.61 (2.34, 8.70) ml to 0.42 (0.15, 1.41) ml and the VRR achieved 84.36 ± 13.87% at 12 months. No nodules regrew throughout the 12-month follow-up period. Of the 11 patients experienced hoarseness due to RLN entrapment before ablation, 7 recovered immediately after separation of the RLN and ZTTN during MWA, 2 recovered after one week, and the other 2 recovered after two months.The RLN is closely related to ZTTN and mainly located at the back of ZTTN. The RLN can be separated from ZTTN by hydrodissection during MWA. US-guided MWA is a safe and effective treatment for ZTTN.© 2024. The Author(s).