To assess the relationship between county-level eviction rates and drug and alcohol mortality rates.Eviction rates from 2003 to 2016 provided by the Princeton University Eviction Lab were merged with Multiple Cause-of-Death Mortality Files and aggregated to the county-year level.All opioid (prescription and heroin), cocaine, psychostimulant, benzodiazepine, antidepressant, and alcohol poisoning-related deaths per 100 000 people, eviction rates, and socioeconomic indicators were merged at the county-year level from 2003 to 2016. We estimated a series of mortality rate models with county and year fixed effects and used a control function (2SRI) method to adjust for the endogeneity of eviction rates.We matched retrospectively collected datasets.Higher levels of eviction rates were consistently associated with higher rates of mortality across six of nine substance categories studied when all counties were combined. Subanalysis by USDA population density measures indicated this positive association was almost entirely driven by urban counties; few systematic associations between the eviction rate levels and mortality were observed for suburban or rural counties.Risk of eviction appears to exacerbate the current "deaths of despair" crisis associated with substance use. Proposed changes to Housing and Urban Development policy that are expected to substantially increase the risk of eviction may worsen an already-acute mortality crisis.