Most COVID-19-associated hospitalizations occur in older adults, but severe disease that requires hospitalization occurs in all age groups, including adolescents aged 12-17 years (1). On May 10, 2021, the Food and Drug Administration expanded the Emergency Use Authorization for Pfizer-BioNTech COVID-19 vaccine to include persons aged 12-15 years, and CDC's Advisory Committee on Immunization Practices recommended it for this age group on May 12, 2021.* Before that time, COVID-19 vaccines had been available only to persons aged ≥16 years. Understanding and describing the epidemiology of COVID-19-associated hospitalizations in adolescents and comparing it with adolescent hospitalizations associated with other vaccine-preventable respiratory viruses, such as influenza, offers evidence of the benefits of expanding the recommended age range for vaccination and provides a baseline and context from which to assess vaccination impact. Using the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET), CDC examined COVID-19-associated hospitalizations among adolescents aged 12-17 years, including demographic and clinical characteristics of adolescents admitted during January 1-March 31, 2021, and hospitalization rates (hospitalizations per 100,000 persons) among adolescents during March 1, 2020-April 24, 2021. Among 204 adolescents who were likely hospitalized primarily for COVID-19 during January 1-March 31, 2021, 31.4% were admitted to an intensive care unit (ICU), and 4.9% required invasive mechanical ventilation; there were no associated deaths. During March 1, 2020-April 24, 2021, weekly adolescent hospitalization rates peaked at 2.1 per 100,000 in early January 2021, declined to 0.6 in mid-March, and then rose to 1.3 in April. Cumulative COVID-19-associated hospitalization rates during October 1, 2020-April 24, 2021, were 2.5-3.0 times higher than were influenza-associated hospitalization rates from three recent influenza seasons (2017-18, 2018-19, and 2019-20) obtained from the Influenza Hospitalization Surveillance Network (FluSurv-NET). Recent increased COVID-19-associated hospitalization rates in March and April 2021 and the potential for severe disease in adolescents reinforce the importance of continued COVID-19 prevention measures, including vaccination and correct and consistent wearing of masks by persons not yet fully vaccinated or when required by laws, rules, or regulations.†.