We investigated the association between serum levels of high-sensitivity C-reactive protein (hs-CRP) and stroke recurrence events in a cohort of patients with acute ischemic stroke (IS). We prospectively studied 286 patients with acute IS who were admitted within 24 h after the onset of symptoms. Serum levels of hs-CRP, and National Institutes of Health stroke scale (NIHSS) were measured at admission. The primary endpoint was stroke recurrence 1 year after stroke onset. We used logistic regression models to assess the relationship between hs-CRP levels and the risk of recurrent stroke. In multivariable models, hs-CRP levels were associated with an increased risk of an NIHSS greater than 6 [odds ratio=1.17; 95% confidence interval (CI)=1.05–1.48; P=0.021]. Among the participants, stroke recurrence was found in 48 (16.8%) cases. In multivariate analyses, the third and fourth quartiles of hs-CRP were significantly associated with stroke recurrence during the observation period compared with the first quartile group (P<0.01). In addition, the hs-CRP level in the highest quartile was associated with a higher risk of stroke recurrence (odds ratio=2.75; 95% CI=1.62–3.92; P=0.006). Hs-CRP (area under the curve=0.71; 95% CI=0.64–0.79) improved the ability of the NIHSS score to diagnose stroke recurrence (area under the curve of the combined model 0.78; 95% CI=0.73–0.84; P<0.01). Serum levels of hs-CRP at admission predicted the future stroke recurrence in patients with IS.