Background: Recurrent and persistent secondary hyperparathyroidism (SHPT) nodules have an incidence of 10-70% after surgery. The treatment of recurrent and persistent SHPT nodules is a challenge, and surgical resection of difficult-to-reach or post-operative adhesions often fails. Purpose: The aim of this research was to study the safety and effectiveness of microwave ablation (MWA) for recurrent and persistent SHPT. Materials and methods: This was a retrospective study of 11 patients enrolled with a total of 16 nodules, and MWA was employed to manage SHPT. The laboratory test results, including the intact parathyroid hormone (iPTH), serum calcium, phosphorus and alkaline phosphatase (ALP) levels, improvement of SHPT-related symptoms after ablation, and complications during and after MWA were recorded and analysed. Results: After ablation the value of iPTH was markedly decreased from 1570 +/- 1765 pg/mL to 287 +/- 239 pg/mL 1 day after MWA (p<0.05). The levels of serum calcium and phosphorus decreased from 2.51 +/- 0.23 mmol/L to 2.06 +/- 0.27 mmol/L (p<0.001) and 1.80 +/- 0.43 mmol/L to 1.48 +/- 0.32 mmol/L (p<0.05), respectively, 1 day after MWA. There was no significant difference in the ALP value before and after MWA (p>0.05). The clinical symptoms, including ostalgia, pruritus, disability, and restless legs, improved after MWA. Minor complications and side effects encountered during or after MWA include haematoma (1/11, 9%), transient hoarseness (2/11, 18.2%), hypocalcemia (6/11, 54.5%). No major complication occurred. Conclusion: MWA may be safe and effective to manage recurrent and persistent SHPT nodules; a definite conclusion needs to expand the sample size with a longer follow-up time.