Vaccination is important for the prevention of coronavirus-induced disease 2019 (COVID-19) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and to protect persons with a high risk for complications. There have been reports of myopericarditis following COVID-19 vaccination, especially in adolescent males and young adults. Breakthrough infections, such as the Delta or Omicron variant of SARS-CoV-2, have raised great concern about the necessity for repeated doses of the vaccine. A case of myopericarditis after the second dose of COVID-19 mRNA-1273 (Moderna) vaccine in a 23-year-old man with a prior episode of viral myopericarditis is presented. He received the second dose of the COVID-19 mRNA vaccine, after which he developed persistent midsternal chest pain and he was subsequently transferred to our emergency department. An echocardiogram showed a trivial inferior pericardial effusion with diffuse left ventricular systolic dysfunction. He was treated with colchicine from the first day of hospitalization with a diagnosis of myopericarditis. His chest pain had resolved by the third day, and left ventricular wall motion was dramatically improved by the seventh day of hospitalization. A strong response to the second vaccination in the present case suggests that the prior history of myopericarditis is evidence of strong congenital or acquired immunological features in this individual. Individuals with such a strong immune response may be more likely to develop myopericarditis after mRNA vaccination. Immunization against COVID-19 is currently recommended from a risk-benefit standpoint. We advised the patient to avoid additional COVID-19 mRNA vaccines because of this episode. The risk of COVID-19 weighed against myopericarditis associated with the mRNA vaccination should be considered on a case-by-case basis. This case may help us better understand the mechanism of myopericarditis following COVID-19 mRNA vaccination.