Object To investigate the efficacy and safety of ultrasound-guided microwave ablation (MWA) in the treatment of primary hyperparathyroidism (PHPT) and evaluate MWA effect on bone metabolism. Methods A total of 20 PHPT patients were treated by MWA in our center from May 2019 to June 2021. The changes of serum parathyroid hormone (PTH), calcium and phosphorus were observed before and after ablation. The markers of bone metabolism, renal function, the volume as well as volume reduction rate of parathyroid lesion were compared before treatment and the last follow-up thereafter. The technical success, complete and partial clinical success rates of treatment were recorded as well. Results At the last follow-up, the median serum PTH and calcium levels in 20 patients decreased significantly compared with that before ablation (P＜0.05). A complete response for both PTH and calcium levels was achieved in 11 of 20 patients, while 7 patients had slightly elevated PTH level only above the upper limit of normal reference range. The total clinical cure rate was 90%. The median level of 25(OH)D at the last follow-up was significantly higher than that before ablation (P < 0.01). The median level of total procollagen type I N-telopeptide as well as β-crosslaps determination was significantly lower than that before ablation (P < 0.01). There was no detectable change in renal function during the follow up period. The ablated volumes were all significantly decreased than before (P＜0.05), and the technical success rate was 66.7%. No serious complications were observed. Conclusions Ultrasound-guided MWA is safe and effective in the treatment of PHPT and can improve bone metabolism.