On August 31, 2021, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr).Viral infections are a common cause of myocarditis, an inflammation of the heart muscle (myocardium) that can result in hospitalization, heart failure, and sudden death (1). Emerging data suggest an association between COVID-19 and myocarditis (2-5). CDC assessed this association using a large, U.S. hospital-based administrative database of health care encounters from >900 hospitals. Myocarditis inpatient encounters were 42.3% higher in 2020 than in 2019. During March 2020-January 2021, the period that coincided with the COVID-19 pandemic, the risk for myocarditis was 0.146% among patients diagnosed with COVID-19 during an inpatient or hospital-based outpatient encounter and 0.009% among patients who were not diagnosed with COVID-19. After adjusting for patient and hospital characteristics, patients with COVID-19 during March 2020-January 2021 had, on average, 15.7 times the risk for myocarditis compared with those without COVID-19 (95% confidence interval [CI] = 14.1-17.2); by age, risk ratios ranged from approximately 7.0 for patients aged 16-39 years to >30.0 for patients aged <16 years or ≥75 years. Overall, myocarditis was uncommon among persons with and without COVID-19; however, COVID-19 was significantly associated with an increased risk for myocarditis, with risk varying by age group. These findings underscore the importance of implementing evidence-based COVID-19 prevention strategies, including vaccination, to reduce the public health impact of COVID-19 and its associated complications.Data for this study were obtained from the Premier Healthcare Database Special COVID-19 Release (PHD-SR), a large hospital-based administrative database. † The monthly * These authors contributed equally to this report. † PHD-SR, formerly known as the PHD COVID-19 Database, is a large U.S. hospital-based all-payer database that includes inpatient and hospital-based outpatient (e.g., emergency department or clinic) health care encounters from >900 geographically diverse, nonprofit, nongovernmental, community, and teaching hospitals and health systems from rural and urban areas. PHD-SR represents approximately 20% of inpatient admissions in the United States.