The CDC National Center for Health Statistics' (NCHS) National Vital Statistics System (NVSS) collects and reports annual mortality statistics using U.S. death certificate data. Because of the time needed to investigate certain causes of death and to process and review death data, final annual mortality data for a given year are typically released 11 months after the end of the calendar year. Provisional data, which are based on death certificate data received but not fully reviewed by NCHS, provide an early estimate of deaths before the release of final data. NVSS routinely releases provisional mortality data for all causes of death and for deaths involving COVID-19.* This report presents an overview of provisional U.S. mortality data for 2021, including a comparison of death rates for 2020 and 2021. In 2021, approximately 3,458,697 deaths occurred in the United States. From 2020 to 2021, the age-adjusted death rate (AADR) increased by 0.7%, from 835.4 to 841.6 per 100,000 standard population. COVID-19 was reported as the underlying cause or a contributing cause in an estimated 460,513 (13.3%) of those deaths (111.4 deaths per 100,000). The highest overall death rates by age occurred among persons aged ≥85 years, and the highest overall AADRs by sex and race and ethnicity occurred among males and non-Hispanic American Indian or Alaska Native (AI/AN) and non-Hispanic Black or African American (Black) populations. COVID-19 death rates were highest among persons aged ≥85 years, non-Hispanic Native Hawaiian or other Pacific Islander (NH/OPI) and AI/AN populations, and males. For a second year, the top three leading causes of death by underlying cause were heart disease, cancer, and COVID-19. Provisional death estimates provide an early indication of shifts in mortality trends and can guide public health policies and interventions aimed at reducing mortality directly or indirectly associated with the pandemic and among persons most affected, including persons who are older, male, or from certain race and ethnic minority groups.