Alcohol and drug overdoses have multiple complex causes. In this article we contribute to the literature that links homelessness, the most extreme form of housing disruption, to accidental SUD-related poisonings. Using plausibly exogenous variation from a state's landlord-tenant policies that influence evictions, we estimated the causal impact of homelessness on SUD-related mortality. We found large effects of homelessness on SUD-related poisonings (for example, a 10 percent increase in homelessness led to a 3.2 percent increase in opioid poisonings in metropolitan areas). Our findings indicate that reducing local homelessness rates from the seventy-fifth to the fiftieth percentile levels could have saved more than 1,900 lives from opioid overdoses across all metropolitan localities in the final year of our study data. We conclude that strengthening the social safety net in terms of housing security could help curb the ongoing SUD-related poisoning epidemic in the US.