IMPORTANCE Drug overdose deaths (DODs) surged with the advent of fentanyl. Recent US reports indicated a decline, but standard surveillance systems do not account for monthly variability or seasonality and require monthly population data to calculate DOD rates.

OBJECTIVE To identify when US DOD rates began to decelerate and to examine patterns by census region, drug type, and demographics.

DESIGN, SETTING, AND PARTICIPANTS This repeated cross-sectional study of DOD rates was conducted from January 2015 to October 2024, using data from the National Center for Health Statistics and US Census Bureau. Decedents included those whose drug poisoning death was classified as unintentional, intentional (suicide or homicide), or undetermined intent, identified by International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes for external overdose causes and T codes for opioids, cocaine, and psychostimulants (eg, methamphetamine).

MAIN OUTCOMES AND MEASURES The main outcome was change in monthly DOD rates nationally and by drug type (opioids, cocaine, or methamphetamine), census region, and demographics. Joinpoint regression evaluated significant shifts in DOD rates applying the weighted bayesian information criterion and 2-sided z tests (α = .05).

RESULTS A total of 800 645 US residents (68.3% male; median age, 42 years [IQR, 33-54 years]) died of drug overdose between January 2015 and October 2024. The national DOD rate increased from 14.54 (95% CI, 14.52-14.55) per 100 000 population in January 2015 to 33.24 (95% CI, 33.15 to 33.33) per 100 000 population in August 2023. From August 2023 to February 2024, the monthly DOD rate declined by -0.36 (95% CI, -0.46 to -0.27) per 100 000 population, accelerating to -0.84 (95% CI, -0.77 to -0.92) per 100 000 population through October 2024 and reaching 24.29 (95% CI, 24.21-24.37) per 100 000 population. Opioid-related DOD rates declined faster than stimulant-related DOD rates (-0.80 [95% CI, -0.74 to -0.87] vs -0.25 [95% CI, -0.23 to -0.27] per 100 000 population). While the national DOD rate peaked in August 2023, rates peaked in the Northeast, Midwest, and South census regions in October 2022 and the West peaked a year later. By late 2023, death rates continued to accelerate among adults aged 55 years or older (0.07 per 100 000 population) and American Indian or Alaska Native (0.02 per 100 000 population), Black or African American (1.70 per 100 000 population), Hispanic or Latino (0.20 per 100 000 population), and multiracial (0.28 per 100 000 population) populations, though the pace of increase was slowing, suggesting a potential inflection point.

CONCLUSIONS AND RELEVANCE In this cross-sectional study, US DOD rates entered a new wave of sustained deceleration in 2023 after 2 decades of increase. This shift may reflect changes in drug markets, treatment access, harm reduction efforts, and population-level risk. Although the decline is encouraging, persistent disparities highlight the need for targeted interventions and improved understanding of the underlying drivers.