BACKGROUND: Cancer is associated with an increased risk of stroke. Tumor cells activate platelets, induce a coagulation cascade, and generate thrombin. The composition of thrombi may reflect the mechanism of thrombosis, aiding the determination of the treatment strategy. Here, we investigated the composition and expression of coagulation factors in the thrombi of patients with cancer-associated stroke. METHODS: Patients with stroke who underwent endovascular thrombectomy between September 2014 and June 2020 and whose cerebral thrombi were obtained were divided into those with cancer-associated stroke (cancer group) and propensity score–matched patients without cancer (control group), using 1:1 matching based on age and sex. Immunohistochemistry was performed of the thrombi, and the composition and expression of coagulation factors were compared between groups. RESULTS: Among the 320 patients who underwent endovascular thrombectomy and who had thrombi obtained, this study included 23 patients with cancer and 23 matched controls. In both groups, the median age was 65 years, and 12 patients (52.2%) were men. Platelet composition was significantly higher in the cancer group than in the control group (median [interquartile range], 51.3% [28.0%–61.4%] versus 9.5% [4.8%–14.0%]; P <0.001). Among coagulation factors, thrombin (26.2% [16.2%–52.7%] versus 4.5% [1.3%–7.2%]; P <0.001) and tissue factors (0.60% [0.34%–2.06%] versus 0.37% [0.22%–0.60%]; P =0.024) were higher and factor X was lower (1.25% [0.39%–3.60%] versus 2.33% [1.67%–4.48%]; P =0.034) in the cancer group. There was a positive correlation between thrombin and platelets in the cancer group (r=0.666; P =0.001) but not in the control group (r=−0.167; P =0.627). CONCLUSIONS: Cerebral thrombi in patients with cancer-associated stroke showed higher proportions of platelets, thrombin, and tissue factors, suggesting their key roles in arterial thrombosis in cancer and providing a therapeutic perspective for preventing stroke in patients with cancer-associated stroke.