BACKGROUND: The development of cerebral infarction is multifactorial, including both environmental and genetic factors. This study assessed the association between fibroblast growth factor (FGF)-related gene polymorphisms and the incidence of cerebral infarction among patients on direct oral anticoagulants (DOACs). METHODS: Patients over 18 years old with atrial fibrillation who were receiving DOACs for cerebral infarction prevention at Ewha Womans University Mokdong Hospital and Ewha Womans University Seoul Hospital were enrolled in this analysis. Twenty-one single nucleotide polymorphisms (SNPs) from FGF1, FGF2, and FGFR1 were examined. In multivariable logistic regression analysis, three models (Model I: demographic factors only, Model II: demographic factors and genetic factors, and Model III: genetic factors and the CHA RESULTS: Among the 536 candidate patients, 21 (3.9 %) experienced cerebral infarction while taking DOACs. From Model I and Model II, age ≥ 75 years and previous thromboembolic event history increased the risk of cerebral infarction. For genetic factors in Model II and III, FGF1 rs1596776 GG, FGFR1 rs6996321 AA, and FGFR1 rs7012413 TT genotypes were associated with a higher risk of cerebral infarction. The area under the receiver operating curve increased from 0.747 (Model I) to 0.822 (Model II) by adding genetic factors, demonstrating better model performance. CONCLUSIONS: This study uncovered the association between FGF-related gene polymorphisms and cerebral infarction among patients with atrial fibrillation undergoing DOAC therapy.