Background: Primary hyperparathyroidism presents with a myriad of symptoms, which range in severity. The cause of these symptoms is not well understood. We sought to determine if the severity of preoperative biochemical abnormalities (calcium, parathyroid hormone, vitamin D levels) correlated with symptomatology in patients undergoing surgical treatment for primary hyperparathyroidism. Study Design: Over 15 months, 229 consecutive patients with primary hyperparathyroidism completed a symptom questionnaire before parathyroidectomy. The symptom profiles of patients with significant hypercalcemia at initial presentation (<11.2 mg/dL) and those with baseline calcium levels (<11.2 mg/dL) were compared. The patients were also categorized based on parathyroid hormone (< or <130 pg/mL) and vitamin D (< or <30 ng/mL) and analyzed in a similar manner. Results: Seventy-eight patients (34%) had a baseline calcium <11.2 mg/dL, but compared with patients with calcium <11.2 mg/dL, only the incidence of nephrolithiasis was more common in those patients with significant hypercalcemia (18% vs 9%, p = 0.04). Conversely, depression, bone or joint pain, and constipation were all significantly more common in patients with calcium <11.2mg/dL (p = 0.006, 0.001, and 0.031, respectively). Patients analyzed based on parathyroid hormone and vitamin D levels showed no significant difference in symptom presentation. Conclusions: These data indicate that the degree of parathyroid hormone elevation and the presence of vitamin D deficiency do not correlate with the presence of symptoms in patients with primary hyperparathyroidism. Significant hypercalcemia was associated with nephrolithiasis, but interestingly, patients with milder hypercalcemia had significantly more depression, bone or joint pain, and constipation, suggesting that these symptoms are likely not mediated by hypercalcemia. © 2011 American College of Surgeons. Published by Elsevier Inc.