There are limited data on the incidence of complications and in-hospital outcomes, in patients with Takotsubo cardiomyopathy (TC), as compared with acute myocardial infarction (AMI). From 2007 to 2014, a retrospective cohort of TC was compared with AMI using the National Inpatient Sample database. Complications were classified as acute heart failure, ventricular arrhythmic, cardiac arrest, high-grade atrioventricular block, mechanical, vascular/access, pericardial, stroke, and acute kidney injury. Temporal trends, clinical characteristics, and in-hospital outcomes were compared. During the 8-year period, 3,329,876 admissions for AMI or TC were identified. TC diagnosis was present in 88,849 (2.7%). Compared with AMI admissions, those with TC were older, female, and of white race. Use of pulmonary artery catheter and mechanical ventilation was higher, but hemodialysis lower in TC. The overall frequency of complications was higher in TC (38.2% vs 32.6%). Complication rates increased in both groups over time, but the delta was greater for TC (23%  vs 43% ) compared with AMI (27% vs 36%). The TC cohort had a higher rate of heart failure (29% vs 16.6%) and strokes (0.5% vs 0.2%), but lower rates of other complications (all p <0.001). In-hospital mortality was lower for TC (2.6% vs 3.1%; p <0.001). TC was an independent predictor of lower in-hospital mortality in admissions with complications. In conclusion, compared with AMI, TC is associated with greater likelihood of heart failure, but lower rates of other complications and mortality. There has been a temporal increase in the rates of in-hospital complications and mortality due to TC.