Ischemic stroke is a complex, multifactorial, and polygenic disease. Reports on relationship between Factor V G1691A single nucleotide gene polymorphism and ischemic stroke have revealed inconsistent results. We conducted an updated meta-analysis to determine the role of Factor V single nucleotide gene polymorphism in ischemic stroke.We searched the literature using academic electronic databases that is, PubMed, Trip Data Base, EBSCO, and Google Scholar, last search up to September 2017. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from fixed or random effects models whichever applicable using software STATA version 13 (StataCorp LP, College Station, TX).Forty case-control studies met the inclusion criteria, which included 6860 cases and 18,025 controls. Altogether, 19 studies in young adults (age < or = 40 years) and 17 studies were conducted in old stroke (age > 40). Four studies did not report the mean age at recruitment. Significant association between Factor V G1691A gene polymorphism and risk of ischemic stroke were observed under dominant model (OR 1.40; 95% CI: 1.22 to 1.62, P value <.001). Stratified analysis suggested substantial association of Factor V gene polymorphism and risk of ischemic stroke in cases with onset at young age (OR 1.84; 95% CI: 1.47 to 2.30), but was not statistical significant in cases at old age (>40 years).Factor V G1691A single nucleotide gene polymorphism was associated with risk of ischemic stroke mainly in young adults. Further research with adequately powered prospective studies in homogenous subjects are required to determine the nature of association in young stroke.