Objective: To assess the feasibility of microwave ablation (MWA) in treating ectopic secondary hyperparathyroidism (SHPT) in patients with chronic renal failure. Methods: In this retrospective study, MWA was used to manage 22 SHPT nodules in 20 patients. The laboratory test results, including intact parathyroid hormone (iPTH), serum calcium, phosphorus and alkaline phosphatase (ALP) levels; clinical symptoms; complications before, at one day after MWA, and at the end of follow-up were recorded and compared. Both echogenicity and size of SHPT nodules on ultrasound were documented before and after MWA. Results: iPTH levels decreased from 1106 +/- 396 pg/mL to 264 +/- 251 pg/mL (p < .001). Serum calcium and phosphorus levels decreased from 2.53 +/- 0.21 mmol/L to 2.14 +/- 0.25 mmol/L (p < .001) and from 1.96 +/- 0.52 mmol/L to 1.76 +/- 0.49 mmol/L (p < .05), respectively. There was no significant change in ALP levels across the different measurements (p = .895). No significant differences were detected in iPTH, serum calcium and phosphorus levels, which were all in the normal range during the follow-up period (3-26 months, mean: 15.49 months) after MWA (p = .186). The echogenicity of SHPT nodules changed from hypoechogenicity to uneven hyperechogenicity with a volume decrease in the majority of the nodules. Mild symptoms of Horner's syndrome occurred in one patient (5%), which improved during the follow-up period. A hematoma was encountered during ablation (5%). Hypocalcemia occurred in four patients one day after MWA (20%). No other complications were associated with MWA. Conclusion: MWA is a feasible option to treat ectopic SHPT nodules for destroying parathyroid gland tissue in ectopic SHPT with long-lasting clinical effects.