Background: This study sought to identify factors contributing to the increase in HIV and STD transmission among African American young adults (AA-YAs) in Mississippi by examining condom use perception and HIV/AIDS and STD knowledge among this group. Over a three year span (2006-2009), Mississippi has seen an increase in HIV and STD infections among this population. The study also examined the extent of condom use, knowledge barriers and attitudes as factors that may contribute to the incidence of HIV and STD infections among AA-YAs. Methods: This study tested the hypothesis that there is no difference among AAYAs in their level of knowledge regarding HIV/AIDS, their attitude toward condom use, their use of condoms, their likelihood of use of condoms, their risk-taking/risk assessment regarding HIV/AIDS. Convenience sampling was used to select the HBCUs to be included in the study. A total of 483 African Americans aged 18 to 24 attending Jackson State University, Alcorn State University, Mississippi Valley State University and Tougaloo College, and clients from My Brother’s Keeper, Inc. were given a questionnaire adopted from the Diffusion of Effective Behavioral Intervention (DEBI). The data collected from the questionnaire were analyzed using descriptive statistics. The independent t-test, ANOVA test were used to test for variances between groups. Results: The results demonstrate that AA-YAs may have knowledge about HIV, but still lack understanding about modes of transmission. Though college students are more knowledgeable, there is still knowledge deficiencies among students attending HBCUs located in rural areas. Males scored slightly higher on HIV/AIDS knowledge compared to females, most young women do not use a condom because they trust their male partner and felt not using condoms would increase the intimacy. Conclusions: Stronger efforts must be made to build the capacity of young people to utilize existing health information to make positive choices.