Intraoperative parathyroid hormone (PTH) monitoring has become an integral adjunct to minimally invasive parathyroidectomy. Guidelines for predicting therapeutic excision of all hyperactive parathyroid tissue have been routinely based on peripheral blood samples drawn at various time intervals. Whether these same guidelines can be used to predict success based on central blood draws has not been established. The authors wanted to evaluate whether peripheral criteria were applicable when PTH levels were drawn from a central location. Simultaneous peripheral venous (PV) and central venous (CV) PTH samples were drawn from 64 patients undergoing cervical exploration for primary hyperparathyroidism. Median preexcision PTH was significantly higher centrally at 165 pg/mL (interquartile range [IQR], 101-391 pg/mL) versus peripherally 102 pg/mL (interquartile range, 73-156 pg/mL, P < 0.0001). Postexcision PTH was slightly greater in CV (38 pg/mL; IQR, 24-62) than in PV (29 pg/mL; IQR, 22-51; P < 0.0001). The decrease in intraoperative PTH was compared after excision of an initial gland. Fifty-four of the 64 patients had all hyperfunctioning parathyroid tissue removed after initial gland resection. Pre- to postexcision ratios for CV and PV were compared using receiver operating characteristic curve methods, and summarized by area under the curve (AUC). PV (AUC = 0.85) appears to be a slightly more sensitive discriminator than CV (AUC = 0.83), although the difference is not statistically significant (P = 0.5). Despite higher absolute values for CV, both peripheral and central sample sites accurately predict outcomes based on established guidelines for intraoperative PTH monitoring.