From 2017 to 2018, the United States experienced a 4.1% decline in drug overdose deaths, with 67,367 deaths recorded in 2018. Of these, 69.5% involved an opioid, with prescription opioids, heroin, and synthetic opioids showing varying trends. Prescription opioid-involved deaths decreased by 13.5%, heroin-involved deaths by 4.1%, and synthetic opioid-involved deaths increased by 10%, driven largely by illicitly manufactured fentanyl. Opioid-involved death rates decreased overall, with the largest declines in Iowa and Ohio, while rates increased in Missouri. The highest opioid-involved death rate was in West Virginia (42.4 per 100,000). Prescription opioid-involved death rates decreased in most regions, with the largest decline in Ohio. Heroin-involved death rates decreased in most regions, with the largest decline in Kentucky. Synthetic opioid-involved death rates increased in most regions, with the largest increase in Arizona. The highest synthetic opioid-involved death rate was in West Virginia (34.0 per 100,000). The findings highlight the need for continued surveillance, prevention, and intervention strategies to address the opioid crisis, particularly synthetic opioids. Efforts to reduce opioid-involved deaths include improving toxicology testing, expanding naloxone distribution, and enhancing treatment access. The report emphasizes the importance of a multisectoral approach to address the complex drug overdose landscape. Limitations include variations in toxicology testing and potential misclassification of race and ethnicity. The findings underscore the need for continued public health efforts to reduce opioid-involved deaths and address emerging threats in the illicit drug supply.From 2017 to 2018, the United States experienced a 4.1% decline in drug overdose deaths, with 67,367 deaths recorded in 2018. Of these, 69.5% involved an opioid, with prescription opioids, heroin, and synthetic opioids showing varying trends. Prescription opioid-involved deaths decreased by 13.5%, heroin-involved deaths by 4.1%, and synthetic opioid-involved deaths increased by 10%, driven largely by illicitly manufactured fentanyl. Opioid-involved death rates decreased overall, with the largest declines in Iowa and Ohio, while rates increased in Missouri. The highest opioid-involved death rate was in West Virginia (42.4 per 100,000). Prescription opioid-involved death rates decreased in most regions, with the largest decline in Ohio. Heroin-involved death rates decreased in most regions, with the largest decline in Kentucky. Synthetic opioid-involved death rates increased in most regions, with the largest increase in Arizona. The highest synthetic opioid-involved death rate was in West Virginia (34.0 per 100,000). The findings highlight the need for continued surveillance, prevention, and intervention strategies to address the opioid crisis, particularly synthetic opioids. Efforts to reduce opioid-involved deaths include improving toxicology testing, expanding naloxone distribution, and enhancing treatment access. The report emphasizes the importance of a multisectoral approach to address the complex drug overdose landscape. Limitations include variations in toxicology testing and potential misclassification of race and ethnicity. The findings underscore the need for continued public health efforts to reduce opioid-involved deaths and address emerging threats in the illicit drug supply.