Female sex workers are especially vulnerable to HIV infection, particularly those who use drugs and engage in street-based sex exchange. This study examines the risk behaviors and HIV serostatus of 806 drug-using female sex workers in Miami and assesses the relative impact of two HIV and hepatitis prevention interventions on changes in risk behavior. Drug-using sex workers were recruited using targeted sampling strategies and were randomly assigned to the NIDA Standard Intervention or an innovative Sex Worker Focused (SWF) Intervention. Outcome analyses indicate that both groups benefited from participation in the intervention trial. However, the SWF Intervention was found to be more efficacious in regard to reductions in unprotected oral sex and sexual violence.