Introduction: Takotsubo cardiomyopathy (TC) causes acute, reversible systolic dysfunction. Clinical variables that predict in-hospital mortality have not been well characterized.Hypothesis: The aim of this study was to determine the in-hospital mortality and clinical predictors of mortality in TC.Methods: Data for this retrospective cohort study were extracted from the Nationwide Inpatient Sample for 2014 using the 9th revision of the International Classification of Diseases (ICD) 429.83 (takotsubo cardiomyopathy). Demographics, in-hospital mortality, conventional risk factors (diabetes, hypertension, hyperlipidemia, alcohol and tobacco abuse), acute illnesses (sepsis, septic shock, stroke, acute respiratory insufficiency, acute renal failure, atrial fibrillation) and chronic conditions (anxiety, depression, malignancy and metastatic diseases) were studied. Univariate and multivariate logistic regression was used to determine predictors associated with inpatient mortality. All analyses were conducted using R 3.4.0 and STATA/MP 14.2. All p-values were two-sided, and statistical significance was determined at the level of p<0.05.Results: A total of 7,375 patients with TC were identified. The mean age was 67 years and patients were predominantly women (92%). Overall in-hospital mortality was 0.8%, with a higher mortality in men (1.6%) compared to women (0.7%). Female patients with TC were more likely to have history of depression (22.6% vs 9.6%; p=0.008) and less likely to have smoking history (18.3% vs 31.5%; p=0.01), compared to male patients. Ethnicity, gender, stroke, acute renal failure, sepsis, anxiety and depression did not predict in-hospital mortality in patients with TC. Atrial fibrillation was an independent predictor of mortality in TC patients on multivariate analysis (adjusted odds ratio [OR] 5.42; 95% confidence intervals 1.18-2.55, p=0.02).Conclusions: Atrial fibrillation appears to be an independent predictor of in-hospital mortality in patients with TC.