The pathophysiology of Takotsubo syndrome (TTS) is incompletely understood. A sympathetic overdrive with coronary microvascular dysfunction might play a central role. The aim of our study was to assess the status of the systemic microcirculation (MC) of patients with TTS, compared to patients with myocardial infarction (MI) and healthy subjects. The systemic microvascular function of 22 TTS patients, 20 patients with MI and 20 healthy subjects was assessed via sublingual sidestream dark-field imaging. In TTS and MI patients, measurements were performed during the acute phase (day 1, 3 and 5) and after 3 months. The measurement in healthy subjects was performed once. The assessed parameters were number of vessel crossings, number of perfused vessel crossings, proportion of perfused vessels, total vessel density and perfused vessel density. The results did not show relevant differences between the investigated groups. Some minor, albeit statistically significant, differences occurred rather randomly. The MC parameters of the TTS group did not show any relevant changes in the temporal course. A systemic microvascular dysfunction could not be identified as a contributing factor in the pathogenesis of TTS. A possible microvascular dysfunction might instead be caused by a local effect restricted to the coronary microvascular bed.