Takotsubo syndrome (TTS) and acute coronary syndrome (ACS) patients have a similar mortality rate. In this study, we sought to determine the short- and long-term outcome of TTS patients as compared to ACS patients both treated with beta-blockers. In the present study we described the data of 5 years of follow up of 103 TTS and 422 ACS patients both treated with beta-blockers. Data from TTS patients were included retrospectively and prospectively, ACS patients were included retrospectively. All retrospectively included patients have been followed up for 5 years. The end point in this study was the occurrence of death. TTS affected significantly more women (87.4%) than ACS (34.6%) (p < 0.01). TTS patients suffered significantly more often from thromboembolic events (14.6% versus 2.1%; p < 0.01) and cardiogenic shock (11.9% versus 3.6%; p < 0.01) than the ACS group. TTS patients had a significantly higher long-term mortality (within 5 years) as compared to ACS patients (17.5% versus 3.6%) (p < 0.01). Patients of the TTS group compared to the ACS group did not benefit from combination of beta-blockers and ACE-inhibitors in terms of long-term mortality (p < 0.01). As we compare TTS patients who were treated with beta-blockers and ACE-inhibitors versus single use of beta-blockers there was no difference in long-term mortality (p = 0.918). TTS patients had a significantly higher long-term mortality (within 5 years) than patients with an ACS.