['Minimally invasive parathyroidectomy for primary hyperparathyroidism is dependent on preoperative localization, commonly with ultrasound and sestamibi imaging. This study sought to determine if preoperative serum calcium and parathyroid hormone (PTH) levels correlate with localization sensitivity and positive predictive value (PPV).', 'This is a retrospective analysis of a prospective database of 1,910 patients with primary hyperparathyroidism from 2002 to 2013, who had surgeon-performed ultrasound and/or sestamibi for preoperative localization. The sensitivity and PPV of ultrasound and sestamibi were analyzed by degree of preoperative serum calcium and parathyroid hormone level perturbation.', 'In 1,910 parathyroidectomy patients, ultrasound was localizing in 1,411 of 1,644 (86%) and sestamibi in 802 of 1,165 (69%) (p < 0.01). The PPV of ultrasound was 1,135 of 1,411 (80%) and sestamibi was 705 of 802 (88%) (p < 0.01). Using logistic regression analysis, there was statistically significant positive correlation between localization and preoperative serum calcium for both sestamibi (odds ratio [OR] 1.21 [95% CI 1.00 to 1.47; p\xa0<\xa00.05]) and ultrasound (OR 1.29 [95% CI 1.03 to 1.60; p < 0.05]). There was a weak, but statistically significant positive correlation of PTH with sestamibi localization (OR 1.00 [95% CI 1.00 to 1.01; p < 0.05]). There was no statistically significant correlation between the PPV and serum calcium or PTH for either study. When patients were divided into quartiles of preoperative serum calcium and PTH levels, localization rates and PPV of both ultrasound and sestamibi increased with higher calcium and PTH levels. Surgeon-performed ultrasound had higher localization rates than sestamibi, with lower calcium and PTH values. Sestamibi demonstrated higher PPV values across all quartiles.'] Does the biochemical severity of primary hyperparathyroidism correlate with the localization accuracy of sestamibi and surgeon-performed ultrasound?