ObjectiveThis study prospectively investigates the association between immunoglobulin G (IgG) N-glycan traits and ischemic stroke (IS) risk. MethodsA nested case-control study was conducted in the China suboptimal health cohort study, which recruited 4,313 individuals in 2013–2014. Cases were identified as patients diagnosed with IS, and controls were 1:1 matched by age and sex with cases. IgG N-glycans in baseline plasma samples were analyzed. ResultsA total of 99 IS cases and 99 controls were included, and 24 directly measured glycan peaks (GPs) were separated from IgG N-glycans. In directly measured GPs, GP4, GP9, GP21, GP22, GP23, and GP24 were associated with the risk of IS in men after adjusting for age, waist and hip circumference, obesity, diabetes, hypertension, and dyslipidemia. Derived glycan traits representing decreased galactosylation and sialylation were associated with IS in men (FBG2S2/(FBG2 + FBG2S1 + FBG2S2): odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.87–0.97; G1n: OR = 0.74, 95% CI: 0.63–0.87; G0n: OR = 1.12, 95% CI: 1.03–1.22). However, these associations were not found among women. ConclusionThis study validated that altered IgG N-glycan traits were associated with incident IS in men, suggesting that sex discrepancies might exist in these associations.