INTRODUCTION: Successful kidney transplantation (KT) is believed to cure secondary hyperparathyroidism, but persistent disease has emerged in a significant number of allograft recipients. Parathyroidectomy (PTX) is ultimately required in some of these patients. AIM: To provide an in-depth analysis of 42 patients who required surgical treatment for persistent hyperparathyroidism after successful renal transplantation and to identify risk factors for PTX present at the time of transplantation. DESIGN: Retrospective case controlled study. METHODS: Charts of 1332 kidney allograft recipients, transplanted between 1989 and 2000, were reviewed. Patients requiring a PTX after a first successful kidney transplantation (serum creatinine < 2.5 mg/dl) were identified. Their charts were checked for various demographic, clinical and biochemical variables. The data were compared with data obtained from a control group closely matched for time of transplantation. RESULTS: Persistent hyperparathyroidism after successful KT requiring PTX occurred in 55 (4.1%) patients. Because of insufficient follow-up data only 42 recipients were eligible for further analysis. The age of the patients was 52 +/- 2.1 years (mean +/- SEM). The time between transplantation and PTX was 416 +/- 61 days. The mean serum creatinine at the time of PTX amounted to 1.6 +/- 0.1 mg/dl. Persistent hypercalcemia, albeit asymptomatic in most patients, was the main indication for PTX. Enlarged parathyroid glands were visualised by ultrasonography in 74% of the cases. Subtotal parathyroidectomy was the procedure of choice. The operative morbidity was negligible and the incidence of persistent or recurrent hyperparathyroidism was low, being 15%. In comparison to the control group, the patients with persistent hyperparathyroidism had a significant longer duration of pre-transplantation dialysis treatment (36.3 vs. 23.0 months, p < 0.01) and significant higher values of intact parathyroid hormone (iPTH) (268.1 vs. 96.0 ng/l, p < 0.001), total serum calcium (10.6 vs. 9.4 mg/dl, p < 0.001), and serum alkaline phosphatases (185.5 vs. 132.0 U/L, p < 0.001) at the time of transplantation. No relationship with the mode of dialysis treatment was observed. CONCLUSION: Persistent hyperparathyroidism requiring PTX after successful KT is a common clinical problem. Patients who spent a long time on dialysis and/or patients with a high pre-transplant level of iPTH, serum calcium and alkaline phosphatases are especially at risk.