BackgroundSocial inequalities among underrepresented communities may lead to higher overdose mortality involving cocaine use. We assessed the temporal trends in cocaine-involved overdose mortality rate in the US by race, ethnicity, and geographic region from 1999 to 2020.MethodsWe conducted a cross-sectional study among adults in the US using data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database (1999 to 2020). To identify cocaine-involved overdose decedents, we used the International Classification of Diseases Code, 10th Revision-T40.5. We used Joinpoint regression to examine the trends in age-adjusted cocaine-involved overdose mortality rates (AAMR) by race, ethnicity, and geographic region and estimated annual percentage changes (APC).ResultsOverall, cocaine-involved overdose mortality trends increased (APC, 11.3%; 95% CI, 0.6, 23.2) from 2017 to 2020. The latest trends have remained stable among Non-Hispanic Whites since 2017 (APC, 4.3%; 95% CI, -5.7%, 15.4%) but have significantly increased among Non-Hispanic Blacks (APC, 27.2%; 95% CI, 22.1%, 32.5%), Hispanics (APC, 26.9%; 95% CI, 20.6%, 33.5%), and American Indians/Alaska Natives (APC, 24.1%; 95% CI, 16.5%, 32.2%).ConclusionCocaine-related overdose deaths in the US significantly increased between 2017 and 2020, but the increase was among racial and ethnic minorities and not among Non-Hispanic Whites. These findings suggest a need to address the US' longstanding racial and ethnic healthcare inequities.