HIV, AIDS, STIs, and unwanted pregnancy continue to impact young adults in the U.S. at a disproportionate rate, particularly during the college years. Attributional style (i.e., locus of control) influences one's HIV risk. Internal locus of control indicates a lower risk of HIV infection, whereas an external locus of control signals an increased risk of HIV. A sample of 1,874 university students aged 16-54 years were surveyed to determine if sexually active males versus females with external, unstable, and specific causal attribution (i.e., external locus of control) engaged in safer sexual practices (e.g., condom use) and lesser alcohol and legal/illicit drug use. Results indicated that male students with an external attributional style engaged in a greater number of unsafe sexual behaviors (e.g., multiple partners) and higher amounts of alcohol and drug use than female students. Additionally, for both males and females, an internal attributional style was associated with greater drug use and a greater likelihood to engage in HIV-related risk behavior. Comprehensive sexual health and substance use education targeting college students should consider attributional style in relation to health promoting and protective behaviors.