Objective To investigate the clinical features of acute ischemic stroke patients with a D-dimer (DD) level of >5 mg/mL.Methods The patients who were hospitalized in our hospital due to acute ischemic stroke from January 2016 to September 2018 were enrolled, and all patients underwent at least two times of DD measurement and had a DD level of >5 mg/mL in at least one measurement. Related clinical data were also collected. The patients were divided into the following subgroups for comparison:one-time DD >5 mg/mL group (DD1 group with 26 patients) and two or more times of DD >5 mg/mL group (DD2 group with 39 patients); tumor group (14 patients) and undefined tumorgroup (51 patients).Results A total of 65 patients were enrolled, among whom 30 (46.2%) were male patients; the patients' age ranged from 46-87 years, with a mean age of 68.7 years. Among these patients, 35 (53.8%) had hypoproteinemia, 30 (46.2%) had anemia, 14 (21.5%) were diagnosed with tumor, and 13 (20%) had poor prognosis. Besides cancer, the definite causes of DD elevation included infective endocarditis, pulmonary embolism, lower extremity venous thrombosis, acidosis, extensive scalds, and femoral neck fracture. There were significant differences between the DD1 group and the DD2 group in DD level, albumin level, hypoproteinemia, and the proportion of patients with suspected tumor markers (P<0.05). There were also significant differences between the tumor group and the undefined tumor group in hemoglobin, sex, anemia, number of risk factors, suspected tumor markers, and the proportion of patients with poor prognosis (P<0.05).Conclusions Malignant tumor is still the most important cause of DD elevation in patients with acute cerebral infarction, andthere is a significant difference between hypercoagulable state due to tumor and non-tumor causes.