Background--The CHA2DS2-VASc score predicts stroke in patients with atrial fibrillation and has been reported to have a prognostic role even in acute coronary syndrome patients. The Takotsubo syndrome is a condition that mimics acute coronary syndrome and may present several complications including stroke. We sought to assess the ability of CHA2DS2-VASc score to predict adverse events in Takotsubo syndrome patients. Methods and Results--Overall, 371 Takotsubo syndrome patients were enrolled in a prospective registry. Patients were divided into 3 groups according to the CHA2DS2-VASc score: Group A (≤1), B (2-3), and C (≥4). The median CHA2DS2-VASc score was 3 (interquartile range: 2-4). Overall, 9%, 42%, and 49% were included in Group A, B, and C, respectively. Follow-up length was 26±20 months. The mortality rate was 6%, 7%, and 17% in Group A, B, and C, respectively (P= 0.011). The stroke rate was 3% and not different among the 3 groups. Estimated major adverse cardiac and cerebrovascular events (the composite of death, myocardial infarction, and stroke) rates in the 3 groups were 6%, 9%, and 17% in Group A, B, and C, respectively (P=0.033). The CHA2DS2-VASc score resulted as a predictor of major adverse cardiac and cerebrovascular events (odds ratio 2.1, 95% confidence interval, 1.2-3.6; P=0.01) and all-cause mortality (odds ratio 1.5, 95% confidence interval, 1.2-1.9; P=0.001). Conclusions--In Takotsubo syndrome, the CHA2DS2-VASc score allows prediction of cardiovascular events and mortality at longterm follow-up.