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Introduction: We previously showed that patients with cancer and acute ischemic stroke (AIS) have higher markers of coagulation, platelet, and endothelial activation, and more circulating microemboli than patients with AIS and no cancer. Herein, we evaluate whether these markers are associated with clinical outcomes in patients with cancer and AIS. Methods: In the MOST-Cancer prospective study, we enrolled 50 adults with active solid-tumor cancer and AIS at 2 New York hospitals from 2016-2020. We collected blood from participants 72-120 hours after stroke onset. We performed a 30-minute transcranial Doppler (TCD) microemboli detection study a median of 4 days after stroke onset. The exposure variables were hematological markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of microemboli on TCD. The primary outcome was a composite of recurrent arterial or venous thromboembolism or death. The secondary outcome was recurrent AIS. We used Cox regression to evaluate individual associations between biomarkers and subsequent outcomes. Results: Median age was 69 years (IQR, 60-76) and 24 participants (48%) were women. The most common cancers were lung (28%) and pancreatic (22%); 86% of participants had distant metastases. During a mean follow-up of 278 days (SD, 367), 43 (86%) participants had the primary outcome of recurrent thromboembolism or death, including 28 (56%) who had recurrent thromboembolism, 13 who had recurrent AIS (26%), and 30 (60%) who died. D-dimer, P-selectin, sICAM-1, sVCAM-1, and microemboli were associated with the composite outcome (Table). Similar results were seen for recurrent AIS. Conclusion: Markers of hypercoagulability and embolic disease were associated with adverse clinical outcomes in cancer-related stroke.