OBJECTIVES: We estimated trends in drug poisoning death rates by educational attainment and investigated educational inequalities in drug poisoning mortality by race, gender, and region. METHODS: We linked drug poisoning death counts from the National Vital Statistics System to population denominators from the Current Population Survey to estimate drug poisoning rates by gender, race, region, and educational attainment (less than high school degree, high school degree, some college, college degree) from 1994 to 2010. RESULTS: There were 372,485 drug poisoning deaths. Education-related inequalities increased during the study among all demographic groups and varied by region. Absolute increases in educational inequalities were higher among Whites than Blacks and men than women. The age-adjusted rate difference between White men with less than a high school degree increased from 8.7 per 100,000 in 1994 to 27.4 in 2010 (change = 18.7). Among Black men, the corresponding increases were 11.7 and 18.3, respectively (change = 6.6). CONCLUSIONS: We found strong educational patterning in drug poisoning rates, chiefly by region and race. Rates are highest and increasing the fastest among groups with less education.