evidence: Semiannual drug overdose death data were obtained from the National Vital Statistics System Multiple Cause-of-Death final (March 2018-December 2020) and provisional files (January-August 2021). These deaths were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes X40–X44 (unintentional) and Y10-14 (undetermined intent). Deaths involving synthetic opioids other than methadone (largely fentanyl or analogs) were identified using code T40.4. Deaths involving psychostimulants with abuse potential other than cocaine (largely methamphetamine) were identified using code T43.6. [...] Drug overdose mortality continued to increase from March to August 2018 through the COVID-19 pandemic for almost all examined subgroups, with increases primarily attributed to fentanyl/analogs and methamphetamine. By March to August 2021, across sexes, the highest drug overdose death rates were among American Indian or Alaska Native men aged 15 to 34 years and Black and American Indian or Alaska Native men aged 35 to 64 years. Within every age and racial and ethnic group, rates were higher in men; for women, and the highest drug overdose death rates were among American Indian or Alaska Native individuals. Limitations of this study are that overdose deaths may be underestimated because of the use of 2021 provisional data3 and that racial or ethnic identification may be misclassified, especially for American Indian or Alaska Native people.5 [...] Published: September 20, 2022. doi:10.1001/jamanetworkopen.2022.32314