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We sought to systematically evaluate diagnostic performance of four-dimensional computed tomography (4D-CT) in the localization of hyperfunctioning parathyroid glands (HPGs) in patients with primary hyperparathyroidism (pHPT). We calculated the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratios (DOR) of 4D-CT on a per-lesion level, as well as pooled sensitivity and positive predictive value (PPV) on a per-patient level with 95% confidence intervals (CIs). Additionally, we plotted summary receiver operating characteristic (SROC) curves and evaluated the areas under the curves (AUC). A total of 16 studies were included in the analysis. Their pooled sensitivity, specificity, PLR, NLR, and DOR of 4D-CT on per-lesion level were 75% (95%CI: 66–82%), 85% (95%CI: 50–97%), 4.9 (95%CI: 1.1–21.3), 0.30 (95%CI: 0.19–0.45), and 17 (95%CI: 3–100), respectively, with an AUC of 81% (95%CI: 77–84%). We also observed heterogeneity in sensitivity (I2 = 79%) and specificity (I2 = 94.7%), and obtained a pooled sensitivity of 81% (95%CI: 70–90%) with heterogeneity of 81.9% (p < 0.001) and PPV of 91% (95%CI: 82–98%) with heterogeneity of 80.8% (p < 0.001), based on a per-patient level. Overall, 4D-CT showed moderate sensitivity and specificity for preoperative localization of HPG(s) in patients with pHPT. The diagnostic performance may improve with 4D-CT's promotion to first-line use on a lesion-based level, further research is needed to confirm the results. [ABSTRACT FROM AUTHOR]