Radiofrequency ablation (RFA) is increasingly recognized as a minimally invasive option for primary hyperparathyroidism (PHPT). This study aimed to evaluate the effectiveness and safety of ultrasound (US)-guided RFA for the treatment of PHPT in Taiwan. We conducted a retrospective study of patients with PHPT who underwent RFA at a single medical center between March 2020 and January 2023. Serum biochemical samples, changes in parathyroid nodule volume, symptomatic scores, and complications were analyzed at follow-up after RFA. The volume reduction ratio (VRR) and treatment response at 1 year were evaluated. Among the 31 patients, 93.55% achieved a complete response with a VRR of 97.48% at 12 months post-RFA. Serum calcium and intact parathyroid hormone (iPTH) levels were significantly lower immediately after treatment than at baseline. However, a difference in phosphorus levels was noted 1 week later, and the alkaline phosphatase (ALP) level was significantly decreased after 3 months (p <
0.05). Transient hoarseness occurred in three patients and resolved spontaneously within 6 months. US-guided RFA is effective and safe for treating PHPT, with a satisfactory VRR and treatment response. This approach could be an alternative to surgery for ineligible patients.