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Objective: This study was conducted to reveal the association of ANGPTL8 gene variant (Rs2278426 (C/T)) with metabolic syndrome in a cohort of Egyptian patients. Materials and methods: This study is a case control study that included 150 patients with metabolic syndrome and 150 healthy control subjects. All subjects were submitted to history taking and thorough physical examination and laboratory analysis. Genomic DNA was extracted and ANGPTL8 gene SNP (rs2278426) was detected by 5’ nuclease assay. The tested genotypes included homozygous genotypes for C allele (CC), homozygous genotypes for T allele (TT) and heterozygous genotypes (CT). Results: A total of 300 subjects were included in the study; group 1 included 150 patients with metabolic syndrome. 21.3% were males and 78.7% were females, and group 2 had 150 healthy subjects. 17.3% were males, and 82.7% were females. In the current study, the metabolic syndrome group showed dysregulation of lipids and fasting plasma glucose (FPG) with a statistically significant increase in body anthropometric measures. There was no statistically significant difference in the distribution of the heterozygous genotype (C/T) relative to the wild-type genotype (C/C) in each of the two tested groups (p = 0.287 and 0.245 in the metabolic syndrome and control groups, respectively). Conclusions: There was no statistically significant difference in the genotype distribution of ANGPTL8 gene variant (Rs2278426) genotypes between the metabolic syndrome and control groups. The homozygous recessive genotype for T allele (TT) was not detected in both tested groups. [ABSTRACT FROM AUTHOR]