IMPORTANCE Educational attainment in the US is associated with life expectancy. As the opioid crisis worsens, it is critical to understand how overdose death rate trends evolve across education groups.

OBJECTIVE To investigate the association between educational attainment and overdose death rates, with emphasis on trends during the COVID-19 pandemic.

DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used National Vital Statistics System Mortality Multiple Cause-of-Death data describing overdose death rates in the US by educational attainment from January 1, 2000, to December 31, 2021, with a focus on 2018 to 2021. Overdose deaths were aggregated by year and educational level for decedents aged 25 years or older.

EXPOSURE Educational attainment, categorized as no high school (HS) diploma, HS diploma (or General Educational Development) but no college, some college but no bachelor's degree, and bachelor's degree or more.

MAIN OUTCOMES AND MEASURES The main outcomes were rates of all overdose deaths, overdose deaths involving opioids, and overdose deaths involving synthetic opioids.

RESULTS Of 912 057 overdose deaths with education information from 2000 to 2021 (mean [SD] age at death, 44.9 [12.3] years; 64.1% male), there were 625 400 deaths (68.6%) among individuals with no college education and 286 657 deaths (31.4%) among those with at least some college. The overdose death rate was 19.9 per 100 000 population. From 2018 to 2021, there were 301 557 overdose deaths, including 58 319 (19.3%) among individuals without an HS diploma, 153 603 (50.9%) among people with an HS diploma, 64 682 (21.4%) among individuals with some college, and 24 953 (8.3%) among individuals with a bachelor's degree. There were 3324 overdose deaths (1.1%) among American Indian or Alaska Native individuals, 2968 (1.0%) among Asian American or Pacific Islander individuals, 49 152 (16.3%) among Black individuals, 31 703 (10.5%) among Hispanic individuals, 211 359 (70.1%) among White individuals, and 3051 (1.0%) among multiracial individuals. From 2018 to 2021, the overdose death rate was 33.4 per 100 000 population, the opioid-related overdose death rate was 24.2 per 100 000 population, and the synthetic opioid overdose death rate was 19.1 per 100 000 population. From 2018 to 2021, the overdose death rate for those without a HS diploma increased by 35.4 per 100 000 population compared with 1.5 per 100 000 population for those with a bachelor's degree. This differential growth was primarily due to increased rates of death involving synthetic opioids.

CONCLUSIONS AND RELEVANCE In this cross-sectional study, lower educational attainment was found to be associated with higher growth in overdose deaths. As the opioid crisis has transitioned to fentanyl and polysubstance use, overdose deaths have become more prevalent in groups with lower socioeconomic status, potentially exacerbating existing life-expectancy disparities.