BACKGROUND: Papillary thyroid microcarcinoma (PTMC) has a high incidence and a good prognosis. Surgical operation for all PTMC might be an overtreatment. The objective of this study was to evaluate the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for treating low-risk PTMC. METHODS: Ninety-eight PTMC in 92 patients were included in this study. US and contrast-enhanced ultrasound (CEUS) examinations were performed before ablation. RFA was performed using the moving-shot technique. The ablation area exceeded the tumor edge to prevent marginal residue and recurrence. Patients were followed at 1, 3, 6, and 12 months and every six months thereafter. US and CEUS examinations were used to evaluate the ablation area. At three months after ablation, US-guided core-needle biopsy (CNB) was performed in the center, at the edge of the ablation area, and in the surrounding thyroid parenchyma to exclude recurrence. RESULTS: The mean tumor volume was 118.8 ± 106.9 mm. The mean volume reduction ratio (VRR) was 0.47 ± 0.27, 0.19 ± 0.16, 0.08 ± 0.11, 0.04 ± 0.10, and 0 at 1, 3, 6, 12, and 18 months after RFA, respectively. Significant differences in the VRR were found between every two follow-up times before six months (p < 0.01), and no significant differences in the VRR were found between six months and after 12 months (p = 0.42). Of all the nodules, 10 (41.7%) resolved in six months, and 23 (95.8%) resolved in 12 months. No residual or recurrent tumor tissue was detected in RFA area or in residual thyroid tissue during follow-up. No suspicious metastatic lymph nodes were detected. The histological pathology results of US-guided CNB confirmed the absence of residual or recurrent tumor. No major complications were encountered. CONCLUSIONS: RFA can effectively eliminate low-risk PTMC with a very small complication rate. RFA may be an alternative strategy for the treatment of PTMC.