Objectives. To contrast the geographic distribution of fentanyl-involved and non–fentanyl-involved fatal overdoses between 2014 and 2018 in Cook County, Illinois.

Methods. We conducted a spatial analysis using locations of fentanyl-involved fatal overdoses (n = 1433) compared with nonfentanyl opioid and polydrug fatal overdoses (n = 1838) collected through the Cook County Medical Examiner’s Office from 2014 to 2018. We also used logistic regression to test significant individual- and neighborhood-level covariates.

Results. Fentanyl overdoses geographically clustered more than nonfentanyl overdoses, and this difference was statistically significant. One area in particular showed significantly elevated risk for fentanyl overdoses (P < .05) located in 2 specific neighborhoods of Chicago. The odds of a fentanyl-involved overdose were significantly increased for men, Blacks, Latinos/as, and younger individuals. Neighborhood deprivation score was the only significant neighborhood-level predictor (odds ratio = 1.11; 95% confidence interval = 1.07, 1.17).

Conclusions. Fentanyl-involved fatal overdoses follow a distinct geographic distribution associated with resource deprivation in neighborhoods where they occur. This suggests an evolving bifurcated drug market, with drug markets in resource-deprived neighborhoods disproportionately likely to include fentanyl.