ObjectivesAssessing the efficacy of single high-intensity focused ultrasound (HIFU) ablation in benign thyroid nodules beyond 12 months.MethodsOne hundred and eight patients underwent single HIFU treatment. Extent of nodule shrinkage [by volume reduction ratio (VRR)] and obstructive symptom score [by 0-10 visual analogue scale (VAS)] were evaluated for 24 months after treatment. VRR (%) was calculated based on the formula: [baseline volume - volume at visit] / [baseline volume] x 100. Binary logistic regression was performed to evaluate factors associated with 24-month treatment success (VRR 50%).ResultsAfter treatment, the mean ( SD) VRR at 3, 6, 12 ,18 and 24 months were 51.32 20.71%, 62.99 22.05%, 68.66 18.48%, 69.76 +/- 17.88% and 70.41 +/- 17.39%, respectively, while the median (IQR) VAS at baseline, 6, 12 and 24 months was gradually lowered from 4.0 (2.0), 2.0 (1.0), 2.0 (1.0) to 1.0 (2.0), respectively. Sixty-three (58.3%) nodules had a further volume reduction (i.e. > 4.5%) from 12 to 24 months, while 22 (20.4%) nodules had a volume increase of > 4.5% from 12 to 24 months. Small pre-ablation nodule volume was a significant determinant for treatment success at 24 months (OR=1.045, 95% CI=1.021-1.092, p = 0.038).Conclusions A majority of nodules had further volume reduction beyond 12 months after single HIFU ablation, but since one-fifth of nodules had a notable volume increase beyond 12 months, a longer period of surveillance would be necessary. Small pre-ablation nodule volume was a significant factor determining 24-month treatment success.Key Points center dot Small but significant nodule shrinkage continues beyond 12 months after single treatment. center dot Obstructive symptom continues to improve beyond 12 months after single treatment center dot Smaller-sized nodules have a greater chance of treatment success at 24 months