The aim of this study is to evaluate the possible role of carbohydrate-antigen(CA)-125 as prognostic marker at short- and long-term follow-up, in subjects with Takotsubo cardiomyopathy (TTC). Sixty-three consecutive subjects with TTC were enrolled in the study and followed for a median 139days. Circulating levels of CA-125, NT-proBNP, and left ventricular ejection fraction (LVEF) were evaluated at admission. Duration of hospital stay, incidence of death, re-hospitalization and recurrence of TTC during follow-up were recorded. The mean hospital stay was 8.3days, adverse events occurred during follow up in 17% of cases. CA-125 levels at admission are inversely related to LVEF (r -0.30, p<0.05) and directly related to hospital stay (r 0.29, p<0.05). CA-125 levels at admission are higher in subjects with adverse events at follow-up (88.9±200.0 vs 20.9±30.0 U/mL, p<0.05). Rates of incidence of adverse events are proportionally increased with CA-125 tertiles (0, 6, 11% respectively, p for trend <0.01), at survival analysis (Log Rank p<0.05) and after correction for age, gender, LVEF and NT-proBNP levels in multivariable Cox analysis (p<0.05). CA-125 levels <10 U/ml are predictors of adverse events at follow up with 91% sensitivity, 52% specificity, 29% positive predictive power, and 96% negative predictive power. Increased CA-125 admission levels are associated with a longer hospital stay, a lower LVEF, and a higher risk of adverse events during follow up. CA-125 might be useful for early risk stratification of subjects with TTC.