The incidence and clinical correlates of acute in-hospital mortality of takotsubo cardiomyopathy (TTC) are not clear. We performed a systematic review and meta-analysis to consolidate the current evidence on acute mortality in TTC. We then assessed the impact of "secondary" TTC, male gender, advancing age, and catecholamine use on mortality. A comprehensive search of 4 major databases (EMBASE, Ovid MEDLINE, PubMed, and Google Scholar) was performed from their inception to the first week of July 2013. We included original research studies, recruiting <10 participants, published in English language, and those that reported data on mortality and cause of death in patients with TTC. Of 382 citations, 37 studies (2,120 patients with TTC) from 11 different countries were included in the analyses. The mean age of the cohort was 68 years (95% confidence interval [CI] 67 to 69) with female predominance (87%). The in-hospital mortality rate among patients with TTC was 4.5% (95% CI 3.1 to 6.2, I2 = 60.8%). Among all deaths, 38% were directly related to TTC complications and rest to underlying noncardiac conditions. Male gender was associated with higher TTC mortality rate (odds ratio 2.6, 95% CI 1.5 to 4.6, p = 0.0008, I2 = 0%) so was "secondary" TTC (risk difference -0.11, 95% CI -0.18 to -0.04, p = 0.003, I2 = 84%). The mean age of patients dying tended to be greater than that in the whole cohort (72 ± 7 vs 65 ± 7 years). In conclusion, TTC is not as benign as once thought. To reduce the mortality rate, greater efforts need to be directed to the diagnosis, treatment, and ultimately prevention of "secondary" TTC.