We analyzed how calcium-lowering medications (CLMs) influenced surgical findings in patients with primary hyperparathyroidism. A retrospective review was conducted of 281 patients undergoing surgery for primary hyperparathyroidism. Logistic regression evaluated the relationship between CLM and surgical findings. A mixed-effects model determined the influence of CLMs on these curves. We found that CLM (P = .018) and a higher serum calcium level (P = .018) were variables making 4-gland hyperplasia less likely. Analysis of intraoperative parathyroid hormone (IOPTH) plots revealed that CLMs altered the kinetics (P = .043). However, the 2 groups did not differ in the number of measurements necessary for a 50% decrease in IOPTH levels. Multivariate logistic regression also revealed that patients taking more than one CLM had an increased association with postoperative hypocalcemia (P = .018). Although CLM contributed to differences in IOPTH curves, their use does not require changing standard IOPTH protocol but should alert the surgeon to the risk of postoperative hypocalcemia.