Background The aim of the present study was to examine the utility of intraoperative parathyroid hormone (ioPTH) monitoring in patients with secondary (2) and tertiary (3) hyperparathyroidism (HPT). Materials and methods We identified 105 patients with 2HPT (n = 33) and 3HPT (n = 72) who underwent ioPTH monitoring during parathyroidectomy. Data are reported as mean±SEM. Results The 2HPT patients underwent 17 subtotal, 10 total, and 6 re-exploratory parathyroidectomies, whereas the 3HPT patients underwent 54 subtotal, 15 limited, and 3 re-exploratory parathyroidectomies. The percent decrease from the baseline ioPTH level at 5, 10, and 15 min after parathyroid resection, respectively, were 72%±3%, 76%±3%, and 76%±3% in patients with 2HPT, and 52%±6%, 60%±4%, and 69%±4% in patients with 3HPT. IoPTH levels failed to drop>50% from baseline in 5 patients (2HPT: n = 2, 3HPT: n = 3) who were normocalcemic at last follow-up. IoPTH did not alter the surgical approach in any 2HPT patients, but did alter management in 25% of 3HPT patients (15 limited resections and 3 supernumerary glands). Normocalcemia was achieved in 97% of 2HPT patients and 99% of 3HPT patients; 2 patients developed recurrent disease. Conclusions Intraoperative PTH levels fell by>50% in nearly 95% of patients with 2HPT and 3HPT, and the PTH level reliably predicted postoperative cure. Although the use of ioPTH did not alter surgical management in any patient with 2HPT, this rapid PTH assay affected the surgical care of a quarter of the patients with 3HPT, and it may prove to be a useful adjunct in this group of patients. © Société Internationale de Chirurgie 2010.