Copyright © 2020 AACE.Objective: Generally recommended treatment options for cystic nodules with compressive symptoms are simple aspiration, percutaneous ethanol injection, or surgery. N-butyl cyanoacrylate (NBCA) is a glue-like substance widely used in neurointerventions, mainly for treating arteriovenous malformations. It obstructs and attaches to the vessel walls, preventing recanalization. Our purpose was to investigate the efficacy and safety of NBCA in volume reduction of benign cystic thyroid nodules with compressive symptoms. Methods: Twenty patients with 21 benign pure or partially cystic nodules were enrolled. After simple cyst aspiration, NBCA/lipiodol mixture was injected within the cyst cavity. Success was defined as at least 50% volume reduction after the intervention. Pre- and postintervention longest diameter and volume (calculated with ultrasonography after measuring three dimensions) of the nodules were compared. Posttreatment measurements were made at the 9-month final visit. Results: Median largest diameter of the nodules measured before and after NBCA treatment was 4.8 cm (min-max, 3.1 and 6.3 cm) and 3.4 cm (min-max, 2.4 and 5.6 cm), respectively. Pre-NBCA treatment median volume was 24.8 mL (min-max, 10.9 and 46.1 mL), whereas posttreatment median volume was 5.5 mL (min-max, 2.1 and 29.6 mL). Median volume reduction was 72.6% (min-max, 21.0 and 95.4%). Intervention was successful in 20 of 21 nodules according to the predefined criteria. The changes in pre- and postintervention median longest diameter and volume were statistically significant. Conclusion: For large cystic thyroid nodules, ablation with NBCA may be an effective treatment choice, as it significantly reduces the cyst volume and prevents fluid re-accumulation. There is need for further studies with a larger number of patients and longer follow-up.