Percutaneous thermal ablation has become an effective, minimally invasive alternative to surgery for managing symptomatic, benign thyroid nodules, providing significant symptom improvement and nodule volume reduction with low rates of complication. Large nodules, typically defined as those exceeding 20 mL, present distinct technical challenges due to their size and proximity to critical structures. Prior studies have shown that percutaneous thermal ablation produces substantial clinical improvement in this subgroup, with 12-month volume-reduction ratios approaching 80 to 90% and continued regression over long-term follow-up. Predictors of favorable response include smaller initial volume, mixed or cystic composition, and the application of staged treatment or marginal-vessel ablation techniques to overcome heat-sink effects. Complications remain uncommon, although large nodules demonstrate a slightly higher risk of nodule rupture, which may present many weeks postprocedure. Transient neuropraxia, hematoma, and procedure-related pain are generally self-limited and mitigated through careful procedural planning and utilizing a moving-shot technique. For patients with multinodular goiter or very large nodules not amenable to percutaneous ablation, thyroid artery embolization has emerged as an additional organ-preserving option with encouraging early outcomes. Overall, thermal ablation, when performed by experienced operators, offers a safe, effective, thyroid-sparing therapy for patients with large benign thyroid nodules.