Tako-tsubo cardiomyopathy (TTC) is an acute reversible cardiac condition usually triggered by stressful events, with a predilection for older women and clinical presentation often confused with acute coronary syndrome. Definition of the diurnal hourly pattern of TTC events may contribute to understanding the pathogenesis of this complex entity. We prospectively enrolled 186 consecutive patients with TTC (68 ± 14 years old, 95% women) and, for comparison, 2,975 patients with ST-segment elevation myocardial infarction (STEMI) at the Minneapolis Heart Institute over the same period. Circadian periodicity was analyzed for hourly occurrence of events throughout the day and for days of the week and months of the year. Occurrence of TTC showed a nonuniform distribution with a distinctive afternoon peak from 12:00 (noon) to 4:00 p.m., comprising 28% (n = 52) of all events, and with the nadir at 12 to 4 a.m. (chi-square 25.6, p <0.001). Patients with events within the peak were older (73 ± 13 years) than other patients (66 ± 13 years, p = 0.0025). Events were uniformly distributed over days of the week and months (p = 0.2 and 0.47, respectively). In contrast, patients with STEMI showed peak occurrence in the early morning hours, 8:00 a.m. to 12:00 p.m., comprising 24% of all events (chi-square 248, p <0.001). In conclusion, TTC events occurred in a circadian pattern with a peak in the afternoon hours, distinctive from the predilection of STEMI for morning hours. This timing of TTC events is most consistent with mechanisms underlying stressful life situations that usually trigger this condition.