The results offer support for the inclusion of protective factors as a standard implementation approach for prevention programs targeted to the reduction of alcohol, tobacco/other drugs (ATOD) use, and HIV risk among sexually active minority adults. The results offer support for a multilevel ecological approach to understanding the relationship between substance use and HIV risk behaviors, reinforcing the effect of risk- and protective-factor framework on adult behaviors. An ecological systems model integrated with a risk and resiliency framework is identified as appropriate to examine the mechanism by which individuals may decrease their engagement in risk behaviors with strengthened protective factors. The ecological systems perspective considers the individual’s behavior and how behavior interacts with the immediate environment and how aspects of larger contextual settings influence the individual and his or her immediate environment. Within this ecological perspective, the objective of this study was to test risk- and protective-factor framework in relation to substance use and HIV-related risks using a latent model analysis among a group of African-American and Hispanic/Latino adults who participated in the center for Substance Abuse Prevention’s 2002-2006 Minority Substance Abuse and HIV/AIDS Prevention Initiative. Figures, references, table