Objective To compare the risk factors between multiple cerebral infarction (MCI) and single cerebral infarction (SCI). This would be beneficial for carrying out corresponding prevention and treatment. Methods We prospectively registered consecutive cases of ischemic stroke in the neurological wards and divided them into two groups: MCI group and SCI group according to their clinical and imaging data. Firstly, the single variable analyses of 24 factors that could be related to the onset of MCI were conducted, and then the multivariate non-condition stepwise logistic regression was performed. Results Significant differences were noted between MCI group and SCI group in terms of age, gender, hpertension, diabetes, heart valvular disease, smoking, cerebral infarction history and first systolic blood pressure after admission. The logistic regression analyses showed that factors of age (OR=1.014, 95%CI 1.003 to 1.026), hypertension (OR=1.566, 95%CI 1.185 to 2.068), smoking (OR=1.473, 95%CI 1.052 to 2.061), cerebral infarction history (OR=1.948, 95%CI 1.326 to 2.864) were independent risk factors for MCI. Conclusion Compared to SCI, age, hypertension, smoking and cerebral infarction history were independent risk factors for MCI patients.