OBJECTIVE: This study examined drug overdose deaths in Mexican-heritage Arizonans, with the goal of informing tailored overdose prevention programs for this community. METHODS: We analyzed death certificate data (from the Arizona Department of Health Services) for drug overdose deaths among Arizona residents from 2018-2022. We compared deaths in US-born and foreign-born Mexican-heritage Arizonans and, as a frame of reference, Non-Hispanic (NH) White Arizonans. We compared demographics, circumstances of death, and mortality rates, using descriptive statistics, multinomial logistic regression models, and age-standardized mortality rates and ratios. RESULTS: The age-standardized drug overdose mortality rate (per 100,000) was lower in the overall Mexican-heritage population (28.0) than in the NH White population (35.9). Nonetheless, the rate in the US-born Mexican-heritage male subgroup (59.5) was higher than in US-born NH White males (49.9) or any other subgroup examined. Synthetic opioids such as fentanyl were involved in higher proportions of deaths among US-born (64.6%) and foreign-born (65.1%) Mexican-heritage Arizonans than among NH White Arizonans (48.5%). In multinomial regression models, the risk of a medical place of death, relative to death at home, was significantly higher in the foreign-born (adjusted Relative Risk Ratio [aRRR] 1.82
95% Confidence Interval [CI], 1.38-2.42) and US-born (aRRR 1.85
95% CI, 1.62-2.11) Mexican-heritage groups than the NH White group, adjusting for age, sex, marital status, county of residence, overdose intent, and drugs involved. CONCLUSIONS: Findings highlight disparate rates of overdose mortality in US-born Mexican-heritage Arizona men, also underscoring racial/ethnic/nativity-based differences in overdose circumstances and decedent characteristics.