Objective: To determine whether patients with tertiary hyperparathyroidism due to single- or two-gland disease undergoing limited resection have similar long-term outcomes compared with patients with hyperplasia undergoing subtotal or total parathyroidectomy. Summary Background Data: Tertiary hyperparathyroidism occurs in less than 2% of patients after renal transplantation. Approximately 30% of these cases are caused by one or two hyperfunctioning glands. Nevertheless, the standard operation for this disease has been subtotal or total parathyroidectomy with autotransplantation. Methods: Seventy-one patients underwent surgery for tertiary hyperparathyroidism. At the time of surgery, 19 patients who had a single or double adenoma underwent limited resection of the enlarged glands only (adenoma group). The remaining 52 patients with three- or four-gland hyperplasia had subtotal or total parathyroidectomy with implantation (hyper group). Long-term cure rates between the two groups were compared. Results: In the adenoma group, 7 patients had a single adenoma and 12 underwent resection of a double adenoma. In the hyper group, 49 patients had subtotal and 3 had total parathyroidectomies. After surgery, 70 of 71 patients (99%) were cured of their hypercalcemia. The incidence of postoperative transient hypocalcemia was significantly higher in the hyper group (27% vs. 5%). No patients in either group had permanent hypocalcemia requiring long-term supplementation. With up to 16 years of follow-up, there have been no recurrences in the adenoma group, whereas three patients (6%) in the hyper group have had recurrent or persistent hyperparathyroidism. Conclusions: Patients with tertiary hyperparathyroidism who underwent limited resection of a single or double adenoma only had equivalent long-term cure rates compared with patients undergoing more extensive resections. Therefore, the authors recommend in patients with tertiary hyperparathyroidism and enlargement of only one or two parathyroid glands that the resection be limited to these abnormal glands only.