The aim of the study was to define the effectiveness and safety of ultrasound-guided percutaneous radiofrequency (RF) thermal ablation in the treatment of compressive solid benign thyroid nodules. Thirty-one patients not eligible for surgery or radioiodine (131I) treatment underwent RF ablation for benign nodules; a total of 33 nodules were treated (2 patients had 2 nodules treated in the same session): 10 cold nodules and 23 hyperfunctioning. Fourteen patients complained of compressive symptoms. Nodule volume, thyroid function and compressive symptoms were evaluated before treatment and at 1, 3 and 6 mo. Ultrasound-guided RF ablation was performed using a Starbust RITA needle, with nine expandable prongs; total exposure time was 6 to 10 min at 95 degrees C in one area or more of the nodule. Baseline volume (measured at the time of RF ablation) was 27.7 +/- 21.5 mL (mean +/- SD), but significantly decreased during follow-up: 19.2 +/- 16.2 at 1 mo (-32.7%; p < 0.001), 15.9 +/- 14.1 mL at 3 mo (-46.4 %; p < 0.001) and 14.6 +/- 12.6 mL at 6 mo (-50.7%; p < 0.001). After treatment, all patients with cold nodules remained euthyroid: five patients with hot nodules normalized thyroid function, and the remaining sixteen showed a partial remission of hyperthyroidism. Besides a sensation of heat and mild swelling of the neck, no major complications were observed. Improvement in compressive symptoms was reported by 13 patients, with a reduction on severity scale from 6.1 +/- 1.4 to 2.2 +/- 1.9 (p < 0.0001). Radiofrequency was effective and safe in reducing volume by about 50% and compressive symptoms in large benign nodules. Hyperfunction was fully controlled in 24% of patients and partially reduced in the others.