Hepatitis A is acquired through the fecal-oral route and is preventable by a safe and effective vaccine. Although hepatitis A is generally mild and self-limited, serious complications, including death, can occur. Since 2016, widespread hepatitis A outbreaks have been reported in 37 U.S. states, primarily among persons who use drugs and those experiencing homelessness. Nearly twice as many hepatitis A-related deaths were reported during 2016-2022 compared with 2009-2015. CDC analyzed data from 27 hepatitis A outbreak-affected states* that contributed data during August 1, 2016-October 31, 2022, to characterize demographic, risk factor, clinical, and cause-of-death data among 315 outbreak-related hepatitis A deaths from those states. Hepatitis A was documented as an underlying or contributing cause of death on 60% of available death certificates. Outbreak-related deaths peaked in 2019, and then decreased annually through 2022. The median age at death was 55 years; most deaths occurred among males (73%) and non-Hispanic White persons (84%). Nearly two thirds (63%) of decedents had at least one documented indication for hepatitis A vaccination, including drug use (41%), homelessness (16%), or coinfection with hepatitis B (12%) or hepatitis C (31%); only 12 (4%) had evidence of previous hepatitis A vaccination. Increasing vaccination coverage among adults at increased risk for infection with hepatitis A virus or for severe disease from infection is critical to preventing future hepatitis A-related deaths.