Abstract Background Previously considered a rare and relatively benign cardiac condition, Takotsubo syndrome (TTS) has undergone a significant shift in perception over the last two decades. This shift was mainly driven by results indicating that TTS is associated with signicant mortality and morbidity. Consequently, also the criteria for diagnosing TTS have been updated to reflect its recognition as a complex, multifactorial disease. Purpose The aim of the present study was to investigate trends in clinical presentation, demographics, and outcomes of patients with TTS. Methods The study analyzed 3,675 patients diagnosed with TTS from 2004 to 2021. Participants were divided into groups based on diagnosis, using three-year intervals, to perform trend analyses on demographics, risk factors, clinical presentations, and outcomes. The Cochran-Mantel-Haenszel test was used for categorical data trends, while the Mann-Kendall test assessed numerical variables. Mortality rates were compared using the log-rank test. Findings: The study period saw a steady increase in male patients (from 10% to 15%, p = 0.003). While apical TTS continued to be the most common type, the occurrence of midventricular TTS increased (from 18% to 37%, p = 0.002). Emotional triggers remained constant, whereas the prevalence of physical triggers significantly rose (from 35% to 50%, p = 0.034). The incidence of cardiogenic shock increased (from 11% to 20%, p=0.030), leading to a rise in in-hospital mortality rates (from 2% to 9%, p<0.001). A landmark analysis showed a significant increase in 60-day mortality rates (p < 0.001), but no difference in one-year mortality over the years (p = 0.140, Figure 1). Summary: This study of temporal trends in TTS highlights a shift in patients demographic with agrowing prevalence among males, increasing recognition of midventricular TTS type, and increased rates of cardiogenic shock and mortality in recent years. This shift aligns with the rising prevalence of physical triggers, as an expression of increased recognition of TTS in association with acute comorbidities.