Objective: To discuss the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels and the short- term prognosis of the patients with acute ischemic stroke. Methods: Two hundred patients with acute ischemic stroke were assessed from May 2015 to November 2015. Clinical data about prognosis of acute stroke patients were obtained at admission. The serum 25(OH)D levels were measured and the NIH Stroke Scale (NIHSS) was evaluated at admission. e outcomes were followed up at the onset of 90 days, carrying on the marks of the Modi ed Rankin Scale (mRS) score. e two groups of data were compared according to mRS score and serum 25(OH)D levels. Results: Two hundred patients were assessed in the study cohort, including 13 cases of lost to follow-up, lost to follow-up rate was 6.5%, a total of 94 cases (47%) in patients with poor prognosis. Lack of serum 25(OH)D group, a total of 165 cases, NIHSS score and mRS score, the urinary inhibition C level, D-dimer level and the average age greater than the not lack of group (P<0.05); 94 patients with poor prognosis in 90 days, 25(OH)D were lower than the prognostic group, atrial brillation, cerebrovascular history, D-dimer, NIHSS score were higher than the prognostic group; multiple factors analysis showed that the serum 25(OH)D levels (OR =0.895, 95% CI 0.840–0.953, P=0.001), hospital NIHSS score (OR =1.811, 95% CI 1.428–2.296, P<0.001) were closely related to the short-term prognosis of acute ischemic stroke. Conclusion: e serum 25(OH)D level is an independent predictor of short-term prognosis of acute cerebral ischemic stroke and is protective factors.