Background: Secondary hyperparathyroidism (SHPT) is a frequently encountered problem in patients with end-stage renal disease (ESRD). Some patients with severe SHPT could not be managed by medical treatment and are ineligible for surgical resection. Purpose: Our objective was to evaluate the efficacy, safety of microwave ablation (MWA) on these patients. Materials and Methods: Between 1 April 2015 and 28 February 2017, 35 patients (M/F 19/16, age 49.8 +/- 12.9 years) were enrolled. All patients were treated with MWA. Levels of intact parathyroid hormone (iPTH) and of serum calcium and phosphorus were compared pre- and post-ablation. Repeated-measures ANOVA was used to compare treatment outcomes pre- and post-ablation. Results: Complete ablation was achieved in all 63 glands in the 35 patients with SHPT. The mean follow-up time was 15.9 +/- 2.2 months. The maximum gland diameter was 6-31 mm (mean, 14.9 +/- 5.5 mm). The trends of the changes in iPTH and calcium levels showed a curve: the level of iPTH and calcium at 6 months post-ablation were lower than those pre-ablation (both p < .0001); after then iPTH remained relatively stable and the end of follow up, with no rebound (p < .0001), while instead of calcium at the end of follow up was not significantly lower than pre-ablation (p = .462). The trend in the change in phosphate levels showed a straight line; the level of phosphate at 6 months post-ablation and at the end of follow up both were significantly lower than pre-MWA (p < .001). There was no major complication. Conclusions: In this series, MWA was used successfully to treat SHPT patients who are ineligible for surgical resection.