Incarcerated adolescents are among the most vulnerable groups for STD infection, and substance abuse is prevalent in over half of this population. Substance abuse and HIV/STD-associated risk behaviors are closely linked among juvenile justice-involved youth, but it is unclear whether common antecedents explain these different problems. The current study examined predictors of HIV/STD risk level and substance use disorders, and investigated whether family variables added unique predictive variance for these problems among incarcerated youth. The sample included 154 substance-involved youth ages 13 to 17 recruited in detention facilities in Miami and Tampa, FL and was primarily male (82%) and African-American (58%). Using a comprehensive assessment strategy with data obtained from youth report, parent report, and laboratory confirmed STD testing, the results show that delinquency is a consistent predictor of both HIV/STD risk level and substance use disorders, and also that substance use directly predicts HIV/STD risk level among incarcerated adolescents. Consistent with previous research, family conflict is an important predictor of substance use disorders even after controlling for other factors. The results suggest the need for integrated family-based interventions addressing delinquency, substance abuse, and HIV/STD-associated risk factors with juvenile justice-involved adolescents.