Background: In Detroit, Michigan, 85% of HIV cases are among African American youth. Approximately 53.4% of African American high school females have had sexual intercourse; 44.7% did not use a condom during the last sexual encounter. School-based sexual health education may be limited regarding HIV prevention. Sexual health education that is culturally and gender-specific is needed to provide knowledge that may impact condom self-efficacy and address the HIV epidemic among African American adolescents in Detroit. Community-based organizations may be used to implement an evidence-based educational intervention. Methods: A 1-group, pretest/posttest design was used to evaluate knowledge of HIV and condom use among 11 African American adolescent females who participated in an evidence-based intervention, Sisters Informing Healing Living Empowering (SIHLE), during 3-hr sessions over 4 consecutive Saturdays. There was 100% attendance among participants for all sessions. Knowledge of HIV and condom use was measured with a 16-item true/false survey before and after the intervention. Results: A significant difference between HIV knowledge at pretest and HIV knowledge at posttest was noted, z = −2.322, p = .02. Conclusion: Nurses and community stakeholders can be instrumental in addressing the HIV epidemic by implementing evidence-based interventions that increase knowledge of HIV prevention and condom use.