ObjectivesPreoperative and intraoperative diagnostic tools influence the surgical management of primary hyperparathyroidism (PHPT), whereby their performance of classification varies considerably for the two common causes of PHPT: solitary adenomas and multiglandular disease. A consensus on the use of such diagnostic tools for optimal perioperative management of all PHPT patients has not been reached.DesignA decision tree model was constructed to estimate and compare the clinical outcomes and the cost-effectiveness of preoperative imaging modalities and intraoperative parathyroid hormone (ioPTH) monitoring criteria in a 21-year time horizon with a 3% discount rate. The robustness of the model was assessed by conducting a one-way sensitivity analysis and probabilistic uncertainty analysis.SettingThe US healthcare system.PopulationA hypothetical population consisting of 5000 patients with sporadic, symptomatic or asymptomatic PHPT.InterventionsPreoperative and intraoperative diagnostic modalities for parathyroidectomy.Main outcome measuresCosts, quality-adjusted life-years (QALYs), net monetary benefits (NMBs) and clinical outcomes.ResultsIn the base-case analysis, four-dimensional (4D) CT was the least expensive strategy with US$10 276 and 15.333 QALYs. Ultrasound and99mTc-Sestamibi single-photon-emission CT/CT were both dominated strategies while18F-fluorocholine positron emission tomography was cost-effective with an NMB of US$416 considering a willingness to pay a threshold of US$95 958. The application of ioPTH monitoring with the Vienna criterion decreased the rate of reoperations from 10.50 to 0.58 per 1000 patients compared to not using ioPTH monitoring. Due to an increased rate of bilateral neck explorations from 257.45 to 347.45 per 1000 patients, it was not cost-effective.Conclusions4D-CT is the most cost-effective modality for the preoperative localisation of solitary parathyroid adenomas and multiglandular disease. The use of ioPTH monitoring is not cost-effective, but to minimise clinical complications, the Miami criterion should be applied for suspected solitary adenomas and the Vienna criterion for multiglandular disease.