Objectives. We examined whether substance-use disorders and poverty predicted first-time homelessness over 3 years. Methods. We analyzed longitudinal data from waves 1 (2001-2002) and 2 (2004~2005) of the National Epidemiologic Survey on Alcohol and Related Conditions to determine the main and interactive effects of wave 1 substance use disorders and poverty on first-time homelessness by wave 2, among those who were never homeless at wave 1 (n :30 558). Firsttime homelessness was defined as having no regular place to live or having to live with others for 1 month or more as a result of having no place of one's own since wave 1. Results. Alcohol-use disorders (adjusted odds ratio [AOR]=1.34), drug-use disorders (AOR=2.51), and poverty (AOR: 1.34) independently increased pro- spective risk for first-time homelessness, after adjustment for ecological vari- ables. Substance-use disorders and poverty interacted to differentially influence risk for first-time homelessness (P