Technetium 99m sestamibi scanning (MIBI) can direct unilateral parathyroidectomy. However, the clinical application remains variable with sensitivities ranging from 55 to 100 per cent. We examined whether patient factors including serum calcium (Ca) and parathyroid hormone (PTH) levels impact the sensitivity of MIBI. We completed a retrospective review of 102 patients with primary hyperparathyroidism and mild hypercalcemia who underwent preoperative MIBI. All patients underwent bilateral neck explorations with abnormalities confirmed by histopathology. MIBI sensitivity was correlated with preoperative Ca and PTH levels using univariate and logistic regression analysis. The mean preoperative Ca was 11.0 mg/dL and the mean PTH was 158 pg/mL. More than 95 per cent of patients with Ca greater than 11.3 mg/dL had a positive scan as compared with 60 per cent of those with lesser values (P = 0.0024). Similarly a serum PTH level greater than 160 pg/mL correlated with positive scans in 93 per cent as opposed to 57 per cent in those with lower levels (P = 0.006). Using a scan-directed approach 65 of 74 patients would have undergone unilateral exploration; this would yield a 7.7 per cent operative failure rate because of contralateral multigland disease. Lower Ca and PTH levels seem to correlate with reduced sensitivity of MIBI. Increasing acceptance of surgery for hyperparathyroidism with minimal hypercalcemia may make MIBI less attractive without ancillary diagnostic measures such as rapid parathormone assays.