Higher plasma total-tau level is associated with incident dementia, but its relationship with stroke risk is unknown. In this prospective community-based study, we evaluated plasma total-tau level as a biomarker of stroke risk in 2,794 Framingham Heart Study participants. Persons with plasma total-tau levels in the top quintile, versus the bottom 4, had an increased risk of incident stroke over a mean follow-up of 8.3 years (hazard ratio = 2.01; 95% confidence interval = 1.32–3.08) following adjustments for age, sex, and stroke risk factors. Our findings demonstrate that plasma total-tau relates to the risk of stroke in a community sample. ANN NEUROL 2019;86:463–467.