Background and Purpose:VIM (vimentin) is a cytoskeletal intermediate filament protein, which has been linked to atherosclerosis and thrombosis; both are important causes of stroke. We examined the relationship between circulating VIM and incidence of stroke, and if carotid plaque could modify the association in a prospective population-based cohort.Methods:This prospective study was based on the Malmö Diet and Cancer Cohort. A total of 4688 participants (39.7% men; mean age, 57.6 years) were examined and blood samples were collected between 1991 and 1994. Incidence of stroke was followed up to 2018. Cox’ proportional hazards regression was used to assess the relationship between VIM and stroke.Results:During a mean follow-up of 22.0 years, a total of 528 subjects were diagnosed with stroke, among which 434 were ischemic stroke. Participants in the highest quartile (vs 1^stquartile) had 1.34× higher risk of total stroke (95% CI, 1.03–1.74) and 1.47× higher of ischemic stroke (95% CI, 1.10–1.98) after adjustment for potential confounders. A significant interaction was found between carotid plaque and VIM with respect to incidence of both total stroke and ischemic stroke (P=0.041 and 0.011, respectively). After stratifying by carotid plaque, high VIM had stronger association with stroke in participants with carotid plaque, especially for the risk of ischemic stroke (adjusted hazard ratio,1.66 [95% CI, 1.23–2.25] for quartile 4 versus quartile 1 to 3).Conclusions:VIM is positively associated with the incidence of stroke, especially in individuals with carotid plaque. Further studies are needed to confirm the observed associations.