This study was designed to clarify the long-term efficacy and safety of percutaneous ethanol injection (PEI) therapy in benign nodular and cystic thyroid diseases, and to evaluate response by criteria defined as disappearance of hot nodule. Solid nodule and complex cyst were classified into three groups in accordance with volume reduction. In autonomously functioning thyroid nodule (AFTN), disappearance of hot nodule with normalization of thyroid hormone level and restored extra-nodular uptake was defined to be curative. In solid nodule (n = 198) and complex cyst (n = 432), initial volume was significantly reduced to post-PEI and final volumes, and volume reduction persisted during follow-up period. Complete response, partial response and no response were as follows: 17.2%, 71.7%, 11.1% in solid nodule; 19.0%, 60.4%, 20.6% in complex cyst, respectively. Differences of volume reduction according to initial volume (> or =10 mL vs. <10 mL) were significant. Correlations between initial and final volumes, and between initial volume and volume reduction were also significant. In 24 patients with AFTN, when effectiveness was assessed by disappearance of hot nodule, only 1 case was curative. Reexpansion or recurrence was observed in 5 cases. Complications developed in 9.0% but there was no permanent or serious complication in this study. In conclusion, our data suggest that PEI therapy could be an effective and safe therapeutic modality for benign nodular and cystic thyroid diseases especially when initial volume is more than 10 mL, but may not induce disappearance of hot nodule itself in AFTN.