We compared the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) and parathyroidectomy (PTX) for the treatment of secondary hyperparathyroidism (SHPT). In this single-center retrospective study, we divided patients into PTX (n = 53) and RFA (n = 47) groups. The primary outcome was the proportion of patients who achieved the target intact parathyroid hormone (iPTH) concentration range (≤ 300 pg/mL). Secondary outcomes were the differences in the changes in iPTH, calcium, and phosphorus levels over time and prognosis. iPTH concentrations of 82.1% and 64.1% in the PTX and RFA groups, respectively, were within the recommended range at the endpoint (P = 0.07). iPTH concentrations in the PTX and RFA groups dropped sharply after treatment (82 ± 163 pg/mL and 280 ± 307 pg/mL, respectively, P < 0.001). There was no difference in the trends of iPTH, calcium, and phosphorus levels between the two groups (P > 0.05). Survival analysis revealed no differences in all-cause mortality and cumulative response rate between the two groups (P = 0.90, P = 0.14, respectively). Notably, the incidence of infection and length of the hospital stay in the RFA group were significantly lower. The preoperative bone-specific alkaline phosphatase concentration was a risk factor for postoperative hypocalcemia. US-guided RFA is minimally invasive and compared to PTX in terms of long-term efficacy and complications in the treatment of severe SHPT in maintenance dialysis patients. It may be used as an alternative technique to PTX; however, further studies are needed.