Objective: To assess the safety and efficacy of ultrasound-guided microwave ablation (MWA) in the treatment of patients who develop secondary hyperparathyroidism (SHPT) after renal transplantation (RT). Methods: In total, nine patients, each with symptomatic SHPT caused by RT and at least one enlarged parathyroid gland, underwent MWA via hydrodissection. Intact parathyroid hormone (i-PTH), serum calcium, serum phosphorus, creatinine and blood urea nitrogen concentrations, before and after MWA, were assessed and compared. Results: Complete ablation was achieved in all patients for a total of 14 ablated parathyroid glands. The mean follow-up time was 17.2 +/- 1.7 months post-operation. The mean maximum diameter of the parathyroid glands was 1.3 +/- 0.4 cm (range: 0.4-2.0 cm). The ablation power implemented was 30 W and the mean time for each parathyroid gland to achieve complete ablation was 287.5 +/- 83.4 s. The mean i-PTH, serum calcium and phosphorus concentrations at one day post-MWA (69.6 pg/mL, 2.23 +/- 0.29 mmol/L, 1.2 2 +/- 0.48 mmol/L, respectively) were significantly lower than those before MWA (780.0 pg/mL, 2.62 +/- 0.32 mmol/L, 1.39 +/- 0.61 mmol/L, respectively; p < .01), whereas the creatinine and blood urea nitrogen concentrations before and after MWA did not differ significantly from each other (p > .05). No significant differences were found between the biomarker concentrations observed at one day post-MWA and at the follow-ups (p > .05). No major operation-related complications occurred. Conclusion: Ultrasound-guided MWA is a safe and effective technique for destroying parathyroid gland tissue in patients who develop SHPT after RT and its clinical effects are long-lasting.