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Introduction: More than a third of large vessel occlusion ischemic strokes do not have clear etiology. Mechanical thrombectomy provides a method to retrieve stroke‐causing thrombi and potentially identifying the etiology. A systematic meta‐analysis is performed to determine if there is a histological difference in red blood cell (RBC) composition of thrombi after the etiology of the stroke is known. Methods: We performed a systematic search through PUBMED and EMBASE. Studies meeting inclusion criteria were identified in which the large vessel occlusion stroke‐causing thrombi histology and etiology of the stroke were determined as either large artery atherosclerotic (LAA), cardioembolic (CE) or cryptogenic. Studies that had the data available or extractable data were selected. Random‐effect models were used to compare the histological difference between each etiology. Results: From inception to August 2021, 4 studies (n = 1022) were used to compare CE vs LAA, 5 studies (n = 1247) were used to compare CE vs cryptogenic and 4 studies (n = 654) were used to compare LAA vs cryptogenic. There was no significant difference in the red blood cells vs white blood cells/fibrin/platelets component between the stroke origins of CE vs LAA (mean difference (MD) ‐1.87; 95% confidence internal [CI]: ‐16.51, 12.78), CE vs cryptogenic (MD 1.18; 95% CI: ‐1.49, 3.86) and LAA vs cryptogenic (MD 7.20; 95% CI: ‐3.93, 18.34). Conclusions: There was no significant gross histological difference between CE, LAA and cryptogenic stroke etiologies and of the large vessel occlusion stroke‐causing thrombi retrieved by mechanical thrombectomy. Further studies into biochemical or genetic markers may be needed to identify stroke etiology.