Abstract Context Radiofrequency ablation (RFA) seems to achieve a significantly larger nodule volume reduction rate (VRR) than laser ablation (LA) in benign nonfunctioning thyroid nodules (BNTNs) Objective To compare the efficacy and safety of both treatments at 12-month follow-up in patients with solid or predominantly solid BNTN. Methods This was a single-center, 12-month, randomized, superiority, open-label, parallel-group trial conducted in an outpatient clinic. Sixty patients with a solitary BNTN or dominant nodule characterized by pressure symptoms/cosmetic problems were randomly assigned (1:1 ratio) to receive either a single session of RFA or LA. Twenty-9 patients per group completed the study. The main outcome measures were VRR and proportion of nodules with more than 50% reduction (technical success rate). Results At 12 months, VRR was 70.9 ± 16.9% and 60.0 ± 19.0% in the RFA and LA groups, respectively (P = .024). This effect was confirmed in the linear regression model that was adjusted for age, sex, nodule baseline volume, and proportion of cellular components (RFA treatment: β = .390; P = .009). No significant between-group difference was observed in the technical success rate at 12 months after treatment. A statistically significant improvement was observed from the baseline to the 12-month follow-up for compression (RFA: 4.6 ± 2.6 and 1.3 ± 0.8, P < .001; and LA: 4.6 ± 2.1 and 1.6 ± 0.8, respectively, P < .001) and cosmetic (RFA: 3.4 ± 0.6 and 1.3 ± 0.5, P < .001; and LA: 3.4 ± 0.5 and 1.4 ± 0.6, P < .001) scores although the between-group differences were not significant. Conclusion RFA achieved a significantly larger nodule volume reduction at 12 months; however, the technical success rate was similar in the RFA and LA groups.