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Background: Stroke severity is mitigated by preceding anticoagulants in acute stroke patients with atrial fibrillation (AF). Such mitigative effects might be different between warfarin and direct oral anticoagulants (DOACs). We compared stroke severity and characteristics in patients who had specific antithrombotics to patients without any prophylactics.Methods: We recruited data from K-PLUS Registry, a regional multicenter stroke registry, between 2009 and 2017. Patients who had AF diagnosed before onset or during hospitalization were included. Background characteristics, stroke severity, and in-hospital death were analyzed according to preceding antithrombotic agents (warfarin, DOACs, antiplatelets aone, or none) at onset.Results: Out of 6,697 participants, 1,765 (median 82 years old) had AF; 526 (30%) were prescribed warfarin, 196 (11%) DOACs, 365 (21%) antiplatelets alone, and 526 (38%) were none. Proportion of patients with CHA2DS2-Vasc score ≥2 was the lowest in patients without anticoagulants (91.7%). Patients taking DOACs were younger (median 79 years), and more frequently resided home. Large lesions were more prevalent in patients with antiplatelets (28%) or those with no antithrombotics (28%) compared to those with DOACs (12%) or with warfarin (21%). NIHSS score was the lowest in patients with DOACs (median 5) compared to those with warfarin (10), antiplatelets (11), or none (13), and in-hospital mortality was also the lowest (4.6%, 6.0%, 9.4%, and 8.0%, respectively). When non-antithrombotics patients were used as a reference, adjusted odds ratio for moderate to severe stroke (NIHSS score ≥16) was 0.53 (95% confidence interval, 0.36-0.77) in those with DOACs, while 0.92 (0.72-1.17) in those with warfarin and 0.94 (0.71-1.23) in those with antiplatelets.Conclusion: In this regional multicenter cohort, preceding DOACs prescription might mitigate stroke severity in AF patients more strongly than other antithrombotics.