Background: Plasma D-dimer level may reflect the activity of thrombus formation in the left atrium of patients with nonvalvular atrial fibrillation (NVAF). Proper anticoagulation with warfarin dramatically decreases the rate of cerebral embolism, reduces stroke severity and subsequent risk of death, as well as the level of D-dimer in NVAF patients. However, the predictive value of D-dimer level on cerebral embolism severity has not been examined. Thus, the purpose of this study was to investigate the association between plasma D-dimer level at admission and infarct size in NVAF patients. Methods: We identified 124 patients with consecutive ischemic stroke and NVAF who were admitted within 48 h of symptom onset. We measured infarction volume from CT taken after 3 ± 1 days from the onset. Plasma D-dimer levels were measured at the time of admission. Relationships were analyzed between infarction volume and plasma D-dimer levels, cardiovascular risk factors, preadmission medications and admission conditions. We also assessed the influence of D-dimer level on functional outcome in patients with preadmission modified Rankin Scale (mRS) score of 0–1 and patients by tertile of D-dimer level (≤0.83, 0.83–2.16 and ≥2.16 µg/ml). Results: Infarction volume significantly correlated with D-dimer level (r = 0.309, p < 0.001), systolic blood pressure (r = 0.201, p = 0.026), diastolic blood pressure (r = 0.283, p = 0.002), National Institutes of Health Stroke Scale (NIHSS) score on admission (r = 0.546, p < 0.001) and mRS score at discharge (r = 0.557, p < 0.001). Multivariate regression analyses showed that the D-dimer level was significantly associated with infarction volume after adjusting for age, sex, current smoker or not, prothrombin time-international normalized ratio ≥1.6, diastolic blood pressure, CHADS2 score and NIHSS score on admission. In patients with a preadmission mRS score of 0–1 (n = 108), D-dimer level was significantly associated with NIHSS score at admission (r = 0.318, p < 0.001) and mRS score at discharge (r = 0.310, p = 0.001). Patients in the highest D-dimer tertile group showed worse outcome than those in the middle (p = 0.041) and lowest (p < 0.001) tertiles. Conclusions: Plasma D-dimer level on admission is significantly related to infarction volume and functional outcome, following cardioembolic stroke in NVAF patients.