Objectives: This study evaluated substance use and HIV risk profile using a latent model analysis based on ecological theory, inclusive of a risk and protective factor framework, in sexually active minority adults (N=1,056) who participated in a federally funded substance abuse and HIV prevention health initiative from 2002 to 2006. Methods: Data were collected locally from community-based organizations using a common baseline instrument that was administered within 30 days of program entry. The latent variables included were social support; neighborhood attachment; family cohesion; intimate abuse; alcohol, tobacco/other drugs (ATOD) use; and HIV risk behaviors. Results: The model-fit indices met acceptable standards for African Americans (CFI = 0.962, TLI = 0.956, RMSEA = 0.033) and for Hispanic/Latinos (CFI = 0.927, TLI = 0.917, RMSEA = 0.047). For African Americans, neighborhood attachment was significantly related to intimate abuse (coefficient = 0.126, p less than 0.01) and family cohesion (coefficient = 0.281, p less than 0.01). Social support was not significantly related to either family cohesion or intimate abuse. Family cohesion was negatively related to ATOD use, which was also related to sex with risk partners and drug-related sex. For Hispanics, neighborhood attachment was significantly related to intimate abuse (coefficient = 0.209, p less than 0.01) and family cohesion (coefficient = 0.209, p less than 0.01). Social support was significantly related to family cohesion (coefficient = 0.274, p less than 0.01), but not related to intimate abuse. Intimate abuse was negatively related to ATOD use. Conclusions: The results support the inclusion of protective factors as a standard implementation approach for prevention programs targeted to the reduction of ATOD use and HIV risk among sexually active minority adults.