We examine the effects of state-level economic conditions including unemployment rates, median house price, median household income, insurance coverage, and annual and weekly work time on deaths on drug overdose deaths including from opioids and prescription opioids between 1999 and 2014. We employ difference-in-differences estimation controlling for state and year fixed effects, state-specific time trends, and demographic characteristics. Drug overdose deaths significantly declined with higher house prices, an effect driven by reduction in prescription-opioid mortality, by nearly 0.17 deaths per 100,000 (~4%) with a $10,000 increase in median house price. House price effects were more pronounced and only significant among males, non-Hispanic Whites, and individuals younger 45 years. Other economic indicators had insignificant effects. Our findings suggest that economic downturns that substantially reduce house prices such as the Great Recession can increase opioid-related deaths, suggesting that efforts to control access to such drugs should especially intensify during these periods.