Takotsubo syndrome (TTS) has been recognized as a benign condition mainly due to its reversibility. However, recent researches have demonstrated that serious cardiac complications could occur during hospitalization. Thus, the aim of this study is to detect factors associated with in-hospital cardiac complications in patients with TTS. A total of 154 consecutive patients with TTS were enrolled retrospectively. In-hospital cardiac complications were observed in 61 patients (40%), including 44 patients with pulmonary edema (29%) and 25 patients with cardiogenic shock (16%). Multivariate logistic regression analysis identified lower systolic blood pressure on admission (OR 0.97, 95% CI 0.96–0.99, p = 0.001), history of diabetes mellitus (OR 2.92, 95% CI 1.01–8.41, p = 0.04), and β-blocker use before admission (OR 16.9, 95% CI 1.57–181.7, p = 0.006) as independent predictors of in-hospital cardiac complications, while chest pain at onset was identified as a negative predictor of cardiac complications during hospitalization (OR 0.20, 95% CI 0.07–0.55, p = 0.001). Patients with cardiac complications more often needed hemodynamic support and longer hospital stay than those without (21.2 ± 19.4 vs. 11.8 ± 16.8 days, p = 0.002). TTS should be no longer recognized as a benign disease, but requiring careful management. We should obtain vital signs and patient’s medical history carefully as soon as possible after admission to predict in-hospital cardiac complications.