Background Stress-induced Tako-tsubo cardiomyopathy (TTC) is an acute cardiac syndrome, mimics ST elevation myocardial infarction (STEMI), largely confined to postmenopausal women, frequently precipitated by a stressful event. The pathogenesis of TTC is still unknown. Some authors hypothesized a possible connection between TTC and anxiety disease, but no previous study analyzed the relationship between anxiety trait and TTC. This study sought to assess the potential role of anxiety trait in the development and clinical course of TTC. Methods We included in the present prospective casecontrol study 50 consecutive patients admitted to our Hospital with a diagnosis of TTC according to the Mayo Clinic criteria. Fifty control patients with anterior STEMI matched for clinical characteristics such as age, gender, and hypertension were selected. During the hospitalization, all patients were asked to complete the Spielberger Trait Anxiety Inventory (STAI) scale for measuring self-reported trait anxiety (Trait-A). Outcome measures at follow-up were death, TTC recurrence, and rehospitalization. Results The mean value of STAI scale was 46 ± 12 in TTC patients and 45 ± 14 in STEMI patients (p = 0.815). High-anxiety trait (STAI scale value C 40) was documented in 30 (60%) TTC patients and in 26 (52%) STEMI patients (p = 0.387). At multivariate analysis, predictors of TTC were lower peak creatine kinase value (HR 0.999; 95% CI 0.998-0.999; p = 0.018) and an antecedent stressful trigger event (HR 45.487;; p = 0.001), but anxiety trait was not. There were no differences in outcome measures between TTC patients with or without high-anxiety trait. Conclusion In TTC patients, high-anxiety trait is a common finding but it is not significantly more frequent than in patients with STEMI. Moreover, a high-anxiety trait seems to be neither associated with a worse clinical outcome nor a predictor of TTC. Our study do not support the routine evaluation of anxiety trait in patients with TTC.