To verify the effectiveness of percutaneous ethanol injection (PEI) in the treatment of thyroid nodules (TN), we analyzed 86 TN from 77 patients before and after one or two sessions of PEI. The medians of the initial and final volumes were: 3.5 mL (range 0.3-82.7) and 1.8 mL (range 0-29.4). Seven percent of the nodules disappeared and the mean nodule size reduction was 52.6% (p< 0.0001). After ethanol injection, the median volume reduction was: 37.3% (range -39.0-82.6) for solid; 53.5% (14.6-88.0) for mostly solid; 58.0% (21.0-64.5) for mixed; 71.0% (18.8-100.0) for mostly cystic and 90.0% (45.9-100.0) for cystic lesions. Furthermore, we compared the variation of the greatest diameter of TN, without any treatment and after PEI, and found this difference statistically significant (p< 0.00001). Pain was the most common complication, although this was mostly described as moderate (27.6%). We conclude that PEI is an efficient and safe treatment option for benign TN.