This study aimed to explore the relationship of D-dimer level with the risk stratification of ischemic stroke, and determine whether high D-dimer levels could be used as a risk factor of ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF). This single-center, retrospective study recruited NVAF patients who did not undergo anticoagulant therapy. These patients were divided into 2 groups: ischemic stroke group and no-stroke group. The medical records of each patient were reviewed, demographic and clinical analyses were performed, and the laboratory results were summarized. A total of 323 eligible in-patients with NVAF, who did not receive anticoagulant therapy, were recruited (206 male and 117 female patients, median age was 75.18 +/- 10.46 years old). Among these patients, 78 patients suffered from acute ischemic stroke. D-dimer level increased with age, and was positively correlated with the risk stratification of stroke, CHADS2 score (rs = 0.441, P < .001), and CHA2DS2-VASC score (rs = 0.412, P < .001), even after adjustment for age and gender (rs = 0.422, P < .001). The difference in baseline D-dimer level between these 2 groups was not statistically significant (0.70 vs 0.66 mg/L, P = .330), but this significantly increased when patients suffered from stroke (1.34 vs 0.70mg/L, P < .001). The D-dimer level after stroke (>= 6 months) was also higher than the baseline (1.16 vs 0.68 mg/L, P = .514) in 6 months, and this level nearly returned to baseline level after one year (0.69 vs 0.68 mg/L, P = .158). However, logistic regression revealed that only the D-dimer level at stroke onset and OMI were independent risk factors for ischemic stroke (P < .001), while the increase from baseline D-dimer levels was not an independent risk factor (P = .125). D-dimer level is positively correlated with the risk stratification of ischemic stroke, but has no predictive value on the occurrence of ischemic stroke in patients with NVAF.