Purpose: Radiofrequency ablation (RFA) and ethanol ablation (EA) are effective and safe for benign symptomatic thyroid nodules (BSTNs). However, relatively little is known about the effects of these procedures on patients’ quality of life (QoL). This prospective, multicenter study evaluated the effects of RFA and EA on changes in thyroid-specific QoL in patients with BSTNs and assessed the volume reduction and safety of these procedures.Methods: Eighty-six consecutive patients with 86 BSTNs were prospectively included from two medical centers. RFA was performed for 55 BSTNs with solidity ≥50% and EA was performed for 31 BSTNs with solidity <50%. QoL was evaluated using an 11-scale, multiple-choice thyroid-specific QoL questionnaire. Nodule characteristics and QoL were evaluated at diagnosis and 1, 6, and 12 months after treatment. Overall QoL was rated from 0 (good) to 4 (poor).Results: The mean longest size and volume of the index nodule were 4.2±1.5 cm and 21.6±22.1 mL, respectively. Patients received 1.1 treatments on average (range, 1 to 2). Significant post-treatment volume reductions were noted; however, the EA group showed a higher volume reduction than the RFA group at 1 (78.7%-16.1% vs. 49.1%-15.8%), 6 (86.3%-21.7% vs. 73.0%-14.5%), and 12 (90.9%-14.9% vs. 80.3%-12.4%) months. The score for each scale of the QoL questionnaire improved significantly during follow-up (all P<0.001). Overall QoL improved significantly, 1.7±0.9 at diagnosis to 0.6±0.7 at the 12-month follow-up (P<0.001). There were no major complications.Conclusion: Both RFA and EA are safe and effective in reducing nodule volume and improving thyroid-specific QoL in patients with BSTNs.