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Introduction Ischemic stroke is a leading cause of mortality and morbidity worldwide. In this age of mechanical thrombectomy, stroke thrombi can be retrieved which can be studied to identify the etiology, and predict angiographic and clinical outcomes, ultimately leading to better devices for recanalization. To identify histological characteristics, we conducted a systematic review and meta-analysis on the relationship between thrombus histology and etiology, and angiographic and clinical outcomes.Methods We searched Pubmed, Embase, and Web of Science databases for articles in English that reported findings related to histologic composition of thrombi in large vessel occlusion ischemic stroke between January 2005 and September 2025. Studies with at least 10 adult patients undergoing mechanical thrombectomy were included. The following associations with histologic composition of thrombi were studied: (1) etiology, (2) angiographic outcome with modified thrombolysis in cerebral infarction (mTICI) scores and first pass effect (FPE), and (3) clinical outcome with modified Rankin Scale (mRS) score.Results A total of 68 studies encompassing 12,255 patients met our inclusion criteria. Among these, 45 studies with 7201 patients identified association between histology of thrombus and etiology of stroke. 23 studies were used for meta-analysis. Studies comparing large artery atherosclerosis (LAA) and cardioembolic (CE) thrombi showed that LAA clots had significantly higher RBC content (mean difference (MD)=7.98, 95% CI 3.91 - 12.05, p=0.0001) but lower fibrin content (MD=-5.51, 95 % CI -9.77 to -1.24, p=0.01) and platelet content (MD -6.82, 95% CI -9.29 to -4.35, p<0.0001). When compared to cryptogenic thrombi, CE clots had almost similar RBC content (MD -0.17, 95% CI -1.79 - 1.4, p=0.84) and platelet content (MD=0.19, 95% CI -2.04 - 2.42, p=0.86) but slightly higher fibrin content (MD=2.68, 95% CI 0.64 to 4.72, p=0.01), 28 studies with 3135 patients identified association between thrombus histology and TICI score. Successful reperfusion (mTICI ≥2b) was associated with higher RBC content (MD=8.56, 95% CI 1.39 to 15.73) and lower fibrin/platelet (MD −4.14, 95% CI −8.12 to −0.17) and WBC content (MD −1.80, 95% CI −3.46 to −0.14). 15 studies with 3770 patients studied association between thrombus histology and FPE. 8 studies (n=2642) used for meta-analysis showed that clots associated with FPE had a higher RBC content (MD=5.77, 95% CI 1.16 - 10.38, p=.014) and lower fibrin content (MD -3.26, 95% CI: -6.54 to 0.02, p<0.05) compared to non-FPE clots. No significant differences were observed for platelet or WBC components. 16 studies with 1736 patients studied association between thrombus histology and mRS score. Five studies (n=464) were included for meta-analysis. RBC-rich thrombi were associated with increased odds of favorable functional outcome (mRS 0-2) (OR 3.42, 95% CI 1.37-8.54, p=0.0085), whereas fibrin-rich thrombi were associated with decreased odds of favorable outcome (OR 0.29, 95% CI 0.12-0.73, p=0.0085).Conclusion This meta-analysis shows that cardioembolic clots are fibrin and platelet rich, while LAA clots are RBC-rich and fibrin-poor. Cryptogenic thrombi are almost identical to CE thrombi which indicates that many cryptogenic strokes may have occult cardiac sources. RBC-rich thrombi leads to better recanalization and clinical outcomes.Disclosures T. Som: None. E. Ren: None.