Objective: We aimed to evaluate and compare the diagnostic performance of ultrasound (US) and 99m-Tc sestamibi scintigraphy for the preoperative localization of primary hyperparathyroidism (PHPT).Methods: This retrospective study was conducted at the Aga Khan University Hospital in Karachi, Pakistan, and comprised the data of patients with PHPT who underwent parathyroidectomy from 2008 to 2017. Preoperative US and 99m-Tc sestamibi scintigraphy findings were recorded and compared to surgical and histological findings, which were taken as a reference standard.Results: The sensitivity of US in the preoperative localization of PHPT was 88.3%, positive predictive value (PPV) was 94.6%, and accuracy was 84.1%. The sensitivity of 99m-Tc sestamibi scintigraphy was 90.4%, PPV was 94.3%, and accuracy was 85.7%.Conclusion: US neck is an efficient tool for the preoperative localization of PHPT, demonstrating a comparable diagnostic yield with 99m-Tc sestamibi, and can serve as a credible first-line imaging modality in a resource-constrained healthcare setup