Background:We examined trends in NAFLD-related mortality in the United States from 1999 to 2022, focusing on sex, racial differences, and specific age groups.Methods:We analyzed age-adjusted mortality rates (AAMRs) for NAFLD-related deaths using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database and assessed differences between sex and racial groups.Results:Between 1999 and 2022, NAFLD-related mortality rose from an age-adjusted mortality rate (AAMR) of 0.2 to 1.7 per 100,000, with an average annual percent change (AAPC) of 10.0% (p< 0.001). In all, 85.4% of the cases were reported after 2008. Females (0.2–2 per 100,000, AAPC: 11.7%,p< 0.001) saw a steeper increase than males (0.2–1.3 per 100,000, AAPC: 9.3%,p< 0.001). White individuals’ AAMR rose from 0.2 to 1.9 per 100,000 (AAPC: 10.8%,p< 0.001). Asian or Pacific Islanders (AAPI) increased from 0.2 in 2013 to 0.5 in 2022 (AAPC: 12.13%,p= 0.002), and American Indians or Alaska Natives (AI/AN) from 1 in 2013 to 2.2 in 2022 (AAPC: 7.9%,p= 0.001). African Americans (AA) showed an insignificant change (0.3–0.5 per 100,000, AAPC: 0.7%,p= 0.498). Regarding age, individuals 45–64 saw AAMR rise from 0.3 to 1.2 per 100,000 (AAPC: 6.5%,p< 0.001), and those 65+ from 0.2 to 6 per 100,000 (AAPC: 16.5%,p< 0.001). No change was observed in the 25–44 age group (AAMR: 0.2 per 100,000, AAPC: 0.0%,p= 0.008).Conclusion:We report increased NAFLD-related mortality among both sexes and certain racial groups. The mortality rate increased for older populations, emphasizing the need for targeted public health measures and evidence-based interventions.