Secondary hyperparathyroidism is a frequent complication of long-term dialysis treatment, and despite recent advances in medical therapy, surgical parathyroidectomy (PTx) is necessary in a considerable number of uremic patients. A prevalence of PTx of 22% was reported in Europe in 1988 in patients on dialysis from 10 to 15 yr, but no large-scale epidemiologic study has been published since then. The aim of the study was to evaluate the prevalence, incidence, and risk factors for PTx in patients on renal replacement therapy (RRT) in Lombardy and to determine whether the incidence has changed over time. The study involved 14,180 patients included in the Lombardy Registry of Dialysis and Transplantation who received RRT for end-stage renal disease (ESRD) between 1983 and 1996. Cox-proportional hazards regression models were used to evaluate the risk factors of PTx, the explanatory covariates being age on admission to RRT, gender, underlying renal disease (nondiabetic or diabetic nephropathy), and dialysis modality (peritoneal dialysis or hemodialysis). The prevalence of PTx in the 7371 ERSD patients who were alive on December 31, 1996, was 5.5% and increased with the duration of RRT (9.2% after 10 to 15 yr, 20.8% after 16 to 20 yr). Similarly, the incidence of PTx increased from 3.3 per 1000 patient-years in patients who had been on RRT for <5 yr to 30 per 1000 patient-years in those receiving RRT for >10 yr. The Cox regression models showed that the relative risk for PTx was significantly higher in women and lower in elderly and diabetic patients. The relative risk for PTx (adjusted for gender, age, and nephropathy) was higher in the patients on peritoneal dialysis than in those on hemodialysis and decreased after transplantation. During the course of a follow-up of 7 yr, the incidence of PTx in patients who started RRT between 1990 and 1992 was no different from that observed in patients who started RRT between 1983 and 1985. In conclusion, the prevalence and incidence of PTx in patients receiving RRT in Lombardy is lower than that in Europe and Italy as a whole, as reported by the 1988 European Dialysis and Transplantation Association Registry; its frequency has not changed significantly during the past few years. The need for PTx decreases markedly after successful transplantation. The epidemiologic finding that the rate of PTx is greater in women, young patients, and individuals who do not have diabetes suggests the need for a more aggressive medical treatment of secondary hyperparathyroidism particularly in such patients.