BACKGROUND: The incidence of Takotsubo syndrome (TTS), also known as the broken heart syndrome or stress cardiomyopathy, is increasing worldwide. The understanding of its prognosis has been progressively evolving and currently appears to be poorer than previously thought, which has attracted the attention of researchers. An attempt to recognize the awareness of this condition among the general population drove us to analyze the dissemination of this topic on TikTok, a popular short-video-based social media platform. We found a considerable number of videos on TTS on TikTok; however, the quality of the presented information remains unknown. OBJECTIVE: The aim of this study was to analyze the quality and audience engagement of TTS-related videos on TikTok. METHODS: Videos on the TikTok platform were explored on August 2, 2021 to identify those related to TTS by using 6 Chinese keywords. A total of 2549 videos were found, of which 80 met our inclusion criteria and were evaluated for their characteristics, content, quality, and reliability. The quality and reliability were rated using the DISCERN instrument and the Journal of the American Medical Association (JAMA) criteria by 2 reviewers independently, and a score was assigned. Descriptive statistics were generated, and the Kruskal-Wallis test was used for statistical analysis. Multiple linear regression was performed to evaluate the association between audience engagement and other factors such as video content, video quality, and author types. RESULTS: The scores assigned to the selected video content were low with regard to the diagnosis (0.66/2) and management (0.34/2) of TTS. The evaluated videos were found to have an average score of 36.93 out of 80 on the DISCERN instrument and 1.51 out of 4 per the JAMA criteria. None of the evaluated videos met all the JAMA criteria. The quality of the relayed information varied by source (All P<.05). TTS-related videos made by health care professionals accounted for 28% (22/80) of all the evaluated videos and had the highest DISCERN scores with an average of 40.59 out of 80. Multiple linear regression analysis showed that author types that identified as health professionals (exponentiated regression coefficient 17.48, 95% CI 2.29-133.52; P=.006) and individual science communicators (exponentiated regression coefficient 13.38, 95% CI 1.83-97.88; P=.01) were significant and independent determinants of audience engagement (in terms of the number of likes). Other author types of videos, video content, and DISCERN document scores were not associated with higher likes. CONCLUSIONS: We found that the quality of videos regarding TTS for patient education on TikTok is poor. Patients should be cautious about health-related information on TikTok. The formulation of a measure for video quality review is necessary, especially when the purpose of the published content is to educate and increase awareness on a health-related topic.