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We aimed to evaluate the pooled incidence of central vein sign on T2*-weighted images from patients with multiple sclerosis (MS), and to determine the diagnostic performance of this central vein sign for differentiating MS from other white matter lesions and provide an optimal cut-off value. A computerized systematic search of the literature in PUBMED and EMBASE was conducted up to December 14, 2018. Original articles investigating central vein sign on T2*-weighted images of patients with MS were selected. The pooled incidence was obtained using random-effects model. The pooled sensitivity and specificity were obtained using a bivariate random-effects model. An optimal cut-off value for the proportion of lesions with a central vein sign was calculated from those studies providing individual patient data. Twenty-one eligible articles covering 501 patients with MS were included. The pooled incidence of central vein sign at the level of individual lesion in patients with MS was 74% (95% CI, 65–82%). The pooled sensitivity and pooled specificity for the diagnostic performance of the central vein sign were 98% (95% CI, 92–100%) and 97% (95% CI, 91–99%), respectively. The area under the HSROC curve was 1.00 (95% CI, 0.99–1.00). The optimal cut-off value for the proportion of lesions with a central vein sign was found to be 45%. Although various T2*-weighted images have been used across studies, the current evidence supports the use of the central vein sign on T2*-weighted images to differentiate MS from other white matter lesions. [ABSTRACT FROM AUTHOR]