It is recommended to get the multiple coronavirus disease 2019 (COVID-19) vaccinations for almost all people including asthma patients. A 70-year-old Japanese woman with asthma experienced worsening of respiratory symptoms after the second dose of the mRNA-based COVID-19 vaccine BNT162b2. The patient had hypercapnic respiratory failure and cardiac-apex ballooning and was diagnosed with takotsubo cardiomyopathy induced by asthma exacerbation. Therapies for asthma exacerbation resulted in prompt improvement of respiratory failure and cardiac-apex ballooning. Our findings suggest that asthma patients are prone to exacerbations after receiving the COVID-19 vaccination; therefore, stratification of the patients at risk is required.