Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) disproportionately burdens African American youth and young adults. In studies conducted in Historically Black Colleges and Universities (HBCU) settings, African American youth generally perceive themselves as having a low risk of contracting HIV and sexually transmitted diseases (STDs) despite having higher rates of unprotected sexual encounters, multiple sex partners, and particularly low rates of HIV testing and awareness of HIV status. These findings position HBCUs in a pivotal role for theory-based research and practice to modify behaviors in order to decrease HIV acquisition risk. Get Students Mobilized and Retooled to Transform (SMART) is an interventional research project in an urban HBCU in a northeastern metropolitan area in the US. The project is designed to assess and then address irresponsible behavior among students on college campuses that leads to illicit drug use, excessive alcohol consumption and underage drinking, and risky sexual behaviors that increase the likelihood of acquiring HIV and STDs. As gender plays a critical role in interventions, this article explores gender similarities and differences to inform the planning and implementation of Get SMART and any subsequent projects that address substance and alcohol use and HIV in an HBCU setting. Survey research was conducted to find similar and different factors that may be valuable in implementing and tailoring evidence-based interventions in a predominantly African American campus setting. Survey results revealed that more young adult women consume alcohol and use marijuana than young adult men. Young adult men were also more likely to be tested for HIV when compared to young adult women.