D-dimers are one of the basic laboratory markers of fibrinolytic system activity. The aim of this prospective study was to detect changes in D-dimer levels in acute stroke patients as a function of the time of artery recanalization and the therapy used. During a 12-month period, 80 acute ischemic stroke patients admitted to the hospital within a 6-h time window were consecutively enrolled in the study. The clinical neurologic examination, brain computed tomography, neurosonologic examination, and biochemical and hematological blood tests (including D-dimers and fibrinogen) were performed on all patients on admission. The control examinations of D-dimer and fibrinogen blood levels were performed 3 (optional), 6, and 24 h after stroke onset. The Mann-Whitney test, Kruskal-Wallis test, ANOVA test, multiple comparison test, and Pearson test were used for statistical evaluation. Application of intravenous thrombolysis significantly increased the D-dimer levels and decreased the fibrinogen level 6 h after stroke onset in comparison with patients treated with antiplatelets or anticoagulants (P < 0.01), with normalization of blood levels over a 24 h period. The use of sonothrombotripsy showed a tendency to increase the D-dimer levels (P = 0.09) with a significant decrease of the fibrinogen level 6 h after stroke onset (P < 0.05). A significant increase in the D-dimer levels was detected in patients with strokes of cardioembolic and atherothrombotic etiologies, and patients with occlusion of cervical or large intracranial arteries (P < 0.05). There was no correlation between the changes in D-dimer or fibrinogen levels and age, gender, time to artery recanalization, risk factors, and the seriousness of neurologic deficits on admission (P > 0.05). D-dimer levels significantly increased during the first 6 h after stroke onset in patients with large artery occlusion and patients treated using intravenous thrombolysis. However, this increase was independent on the time of artery recanalization thus cannot be used as its marker.