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Previous epidemiologic evidence suggests a protective effect of Toxoplasma gondii infection against multiple sclerosis (MS) development; however, inconsistent findings have been reported in this regard. Therefore, we performed an updated meta-analysis of observational studies to investigate the association of To. gondii infection with MS development. We searched all articles published in PubMed, Scopus, Embase and Web of Science databases as of 20 December 2021. A random effects meta-analysis model was used to generate the pooled OR at 95% CIs. The heterogeneity between studies was assessed using I 2 and Cochran's Q statistics. Moreover, the likelihood of publication bias was determined by Egger's regression test. A total of 11 studies were eligible for meta-analysis, including 1172 MS cases and 1802 controls. Our findings indicated that 29.8% (95% CI 22.8 to 37.2%) of MS patients were seropositive for To. gondii infection, compared with 34.2% (95% CI 21.9 to 47.6%) of control subjects. The estimated pooled OR was 0.79 (95% CI 0.49 to 1.26), suggesting a non-significant negative association between To. gondii infection and MS development (p>0.05). The current study does not support the significant protective role of To. gondii infection on MS development. Our findings imply that further well-designed epidemiological and mechanistic studies are warranted to ascertain the possible association between To. gondii infection and MS and to exclude the potential confounders. [ABSTRACT FROM AUTHOR]