BackgroundIschemic stroke with active cancer is thought to have a unique mechanism compared to conventional stroke etiologies. There is no gold standard guideline for secondary prevention in patients with cancer-related stroke, hence, adequate type of antithrombotic agent for treatment is controversial.MethodsSubjects who were enrolled in National Health Insurance System Customized Research data during the period between 2010 and 2015 were observed until 2019. Subject diagnosed with ischemic stroke within six months before and 12 months after a cancer diagnosis was defined as cancer-related stroke patient. To solve immeasurable time bias, the drug exposure evaluation was divided into daily units, and each person-day was classified as four groups: antiplatelet, anticoagulant, both types, and unexposed to antithrombotic drugs. To investigate bleeding risk and mortality, Cox proportional hazards regression model with time-dependent covariates were used.ResultsTwo thousand two hundred eighty-five subjects with cancer-related stroke were followed and analyzed. A group with anticoagulation showed high estimated hazard ratios (HRs) of all bleeding events compared to a group with antiplatelet (major bleeding HR, 1.35; 95% confidence interval [CI], 1.20–1.52;p< 0.001). And the result was also similar in the combination group (major bleeding HR, 1.54; 95% CI, 1.13–2.09;p= 0.006). The combination group also showed increased mortality HR compared to antiplatelet group (HR, 1.72; 95% CI, 1.47–2.00;p< 0.001).ConclusionsBleeding risk increased in the anticoagulant-exposed group compared to antiplatelet-exposed group in cancer-related stroke patients. Thus, this result should be considered when selecting a secondary prevention drug.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12883-023-03208-4.