Aim The purpose of this study was to explore the influence of serum non-high-density lipoprotein cholesterol (non-HDLC) on neurologic impairment in patients with acute ischemic stroke and its clinical value in disease risk assessment. Methods A total of 611 cases of acute ischemic stroke patients were recruited in this study. NIHSS(National Institute of Health stroke scale), CSS(China Stroke scale), ESS(Europe Stroke Scale) and BI(Barthel Index) were used to evaluate the degree of neurologic impairments. Fasting plasma glucose(FPG), hypersensitive c-reactive protein(hs-CRP), glycosylated hemoglobin (HbA1c), homocysteine (Hcy), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDLC) were measured in all the patients. Then the density of non-HDLC were calculated with the formula of TC minus HDLC. Results Patients with high level of serum non-HDLC had bigger body mass index, higher NIHSS, CSS and BI scores, lower ESS and elevated TC, TG, LDLC, Hcy, FPG, HbA1c, lower HDLC levels. The NIHSS scores changed corresponding with serum non-HDLC level in acute ischemic stroke patients, the total scores of NIHSS, CSS were positively correlated with the serum non-HDLC level, and the total scores of ESS, and BI were negatively correlated with it. High serum level of non-HDLC was an independent risk factor for neurologic impairment in patients with acute ischemic stroke, when serum non-HDLC elevated to borderline high level, the risk of neurologic impairment significantly increased. Conclusion Increased serum non-HDLC level was an independent risk factor of neurologic impairment in patients with acute cerebral ischemia, it would be an effective indicator, and target of the prevention and treatment as well, of risk prediction for neurologic impairment in patients with acute cerebral ischemia.