Objective · To evaluate the significance of B-type natriuretic peptide (BNP) in choice of antithrombotic therapy for acute cerebral infarction patients with atrial fibrillation. Methods · Clinical data of 714 acute cerebral infarction patients with atrial fibrillation were retrospectively analyzed. The patients were divided into two groups according to the cut-off value of BNP (912.5 pg/mL, the 95th quantile). Each group was subdivided into antiplatelet group and anticoagulant group. National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores of patients at admission and day 21 after treatment were compared, and the incidence rates of complication, such as intracranial hemorrhage, symptomatic intracranial hemorrhage, gastrointestinal bleeding, recurrent infarction, deep vein thrombosis, and the mortality were also compared. Results · In BNP>912.5 pg/mL group, the improved rates of NIHSS (P=0.015) and mRS (P=0.031) of anticoagulant group were higher than those of antiplatelet group. The mortality and the incidence of cerebral infarction recurrence in antiplatelet group were higher than those in anticoagulant group, with no statistical significance. The incidences of all kinds of bleeding, intracranial hemorrhage, symptomatic intracranial hemorrhage, gastrointestinal bleeding, and deep vein thrombosis had no significant difference between the two groups. For those with BNP≤912.5 pg/mL, the differences of improved rate of NIHSS and mRS between the two groups were not statistically significant. The mortality and the incidence of cerebral infarction recurrence in antiplatelet group were higher than those in anticoagulant group without statistical significance. The incidences of all kinds of bleeding, intracranial hemorrhage, symptomatic intracranial hemorrhage, gastrointestinal bleeding, and deep vein thrombosis were not significantly different between the two groups. Conclusion · Acute cerebral infarction patients with atrial fibrillation and BNP>912.5pg/mL may benefit more from anticoagulants than antiplatelet agents.