Objective To compare the clinical outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA) in the treatment of primary hyperparathyroidism (pHPT). Method This retrospective study included 104 pHPT patients treated by MWA or RFA between January 2015 and March 2020 in four centers. The clinical outcomes including effectiveness and complications were compared between the two groups. Ablation cure was defined as the reestablishment of normal values of serum calcium and intact parathyroid hormone (iPTH) at least more than 6 months. Clinical cure was defined as the reestablishment of normal values of serum calcium and iPTH throughout the entire follow-up period. Results A total of 77 patients underwent MWA (mean age, 55.5 +/- 16.4 years) and 27 underwent RFA (mean age, 58.9 +/- 15.6 years). During the follow-up (median, 18.7 months in the MWA group; 12 months in the RFA group), no difference was observed between ablation cure rates (88.3% vs. 88.9%, p = 1.000), clinical cure rates (87.0% vs. 82.3%, p = .880), recurrent pHPT (5.2% vs. 3.7%, p = .447), persistent pHPT (11.7% vs. 11.1%, p = 1.000) and complication rate (9.1% vs. 3.7%, p = .677). A maximum diameter less than 0.7 cm was an independent prognostic factor of uncured pHPT in ablation (hazard ratio, 0.1; 95% confidence interval: 0.02, 0.54; p = .007). Major complication - voice change encountered in five patients (6.5%) in the MWA group and in one patient (3.7%) in the RFA group. Conclusion Both RFA and MWA are safe and effective techniques for patients with pHPT, with comparable clinical outcomes.