Background: Hyperactive thyroid nodules (HTN) are usually treated with radioactive iodine (RAI). However, as RAI is associated with a 30-60% long-term risk of permanent hypothyroidism, radiofrequency ablation (RFA) may be a good alternative. Primary aim of this study was to assess the percentage of patients achieving euthyroidism after RFA. Patients and Methods: Patients with a symptomatic HTN were treated by ultrasound-guided RFA, using the trans-isthmic approach and moving-shot technique, in an outpatient setting under local anaesthesia. Results: Twenty-one patients were included, ranging in age from 37-75 years. Follow-up was at least one year. All patients had a suppressed serum thyroid-stimulating hormone (TSH), with free thyroxine (FT4) and free triiodothyronine (FT3) concentrations mildly elevated in 33% and 43% of cases, respectively. RFA was not associated with clinically meaningful adverse effects. TSH normalisation was achieved in 11/21 patients (52%) after first RFA. A partial response, defined as a normalisation of FT4 and FT3, but incomplete improvement of TSH, was observed in 6/21 patients (29%). Three patients had no response (14%), and one patient developed mild, asymptomatic subclinical hypothyroidism. Five patients underwent a second RFA and this led to TSH normalisation in four, thereby raising the rate of complete remission to 71%. Recurrence of TSH suppression did not occur during the study period. Conclusion: These data suggest that RFA is a safe and promising treatment for symptomatic hyperactive thyroid nodules, with a low risk of permanent hypothyroidism. Long-term studies are needed to identify the recurrence risk of hyperthyroidism.