Background: Takotsubo Syndrome (TTS) is characterized by acute and reversible left ventricular dysfunction with apical ballooning arising during acute stress situations. Acute Ischemic Stroke (AIS) is one of the known triggers to TTS, however, the impact of TTS on in-hospital outcomes of AIS remains unexplored. Methods: We utilized data from the National Inpatient Sample (2007-2014) and using ICD-9-CM diagnosis codes to identify admissions for AIS with TTS and evaluated the temporal trends, baseline characteristics, in-hospital complications, length of stay (LOS) and all-cause mortality. Survey multivariable logistic regression was used to compute adjusted Odds Ratios (OR and 95% confidence intervals (CI). Results: An estimated 2,242 (0.4%) TTS cases were identified among AIS hospitalizations (N=43,92,471). The frequency of TTS was higher in elderly, whites and females (82.2%). After adjustment for confounders, TTS incidence in AIS was associated with higher odds of in-hospital complications including cardiogenic shock (OR8.84, CI:4.07-19.17, p<0.001), cardiac arrest (OR3.17, CI:1.57-6.42, p=0.001), and venous thromboembolism (OR1.68, CI:1.14-2.47, p=0.008). Moreover, AIS hospitalizations with TTS showed higher odds of developing respiratory failure (OR3.13, CI:2.42-4.05, p<0.001) and required mechanical ventilation/intubation (OR4.09, CI:3.14-5.32, p<0.001) more frequently compared to non-TTS cohort. The AIS-TTS cohort had longer LOS (8.59 vs 5.22 days) and the mortality was doubled (10.2% vs 5.1% p<0.001) compared to those without TTS. Conclusion: The prevalence of TTS in AIS remained ~20 times higher than the general inpatient population and it predisposed AIS patients to worse inpatient outcomes. Further studies are needed to evaluate the impact of TTS on long-term outcomes in AIS.