There is limited data on the in-hospital outcomes of cardiogenic shock (CS) secondary to takotsubo syndrome (TS). We aimed to assess the incidence, predictors, and outcomes of CS in hospitalized patients with TS. All patients with TS were identified from the National Inpatient Sample database from September 2006 to December 2017. The cohort was divided into those with versus without CS and logistic regression analysis was used to identify predictors of CS and mortality in patients admitted with TS. A total of 260,144 patients with TS were included in our study, of whom 14,703 (6%) were diagnosed with CS. In-hospital mortality in patients with CS was approximately six-fold higher compared with those without CS (23% vs 4%, p <0.01). TS patients with CS had a higher incidence of malignant arrhythmias like ventricular tachycardia or ventricular fibrillation (15.0% vs 4%, p <0.01) and non-shockable cardiac arrests (12% vs 2%, p <0.01). Independent predictors of CS were male gender, Asian and Hispanic ethnicity, increased burden of co-morbidities including congestive heart failure, chronic pulmonary disease, and chronic diabetes. Independent predictors of mortality were male gender, advanced age, history of congestive heart failure, chronic renal failure, and chronic liver disease. In conclusion, CS occurs in approximately 6% of patients admitted with TS, in-hospital mortality in TS patients with CS was approximately six-fold higher compared with those without CS (23% vs 4%, p <0.01), male gender and increased burden of co-morbidities at baseline were independent predictors of CS and mortality.