ObjectiveTo determine the role of circulating microvesicles (MV) on long-term cardiovascular outcomes after stroke, we measured them in patients with first-ever stroke with a 3-year follow-up.MethodsIn the Prospective Cohort With Incident Stroke Berlin (PROSCIS-B), patients with first-ever ischemic stroke were followed up for 3 years. The primary combined endpoint consisted of recurrent stroke, myocardial infarction, and all-cause mortality. Citrate-blood levels of endothelial MV (EMV), leukocyte-derived MV (LMV), monocytic MV (MMV), and platelet-derived MV (PMV) were measured with flow cytometry. Kaplan-Meier curves and adjusted Cox proportional hazards models were used to estimate the effect of MV levels on the combined endpoint.ResultsFive hundred seventy-one patients were recruited (median age 69 years, 39% female, median NIH Stroke Scale score 2, interquartile range 1–4), and 95 endpoints occurred. Patients with levels of EMV (adjusted hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.2–4.9) or LMV (HR 3.1, 95% CI 1.4–6.8) in the highest quartile were more likely to experience an event than participants with lower levels with the lowest quartile used as the reference category. The association was less pronounced for PMV (HR 1.7, 95% CI 0.9–3.2) and absent for MMV (HR 1.1, 95% CI 0.6–1.8).ConclusionHigh levels of EMV and LMV after stroke were associated with worse cardiovascular outcome within 3 years. These results reinforce that endothelial dysfunction and vascular inflammation affect the long-term prognosis after stroke. EMV and LMV might play a role in risk prediction for stroke patients.ClinicalTrials.gov IdentifierNCT01363856.Classification of EvidenceThis study provides Class II evidence of the effect of MV levels on subsequent stroke, myocardial infarction, or all-cause mortality in survivors of mild stroke.