Objective: College students are a high-risk population for new human immunodeficiency viruses (HIV) diagnoses. Although condom use self-efficacy and HIV knowledge can protect against risky sexual behavior (RSB), these same protective factors have been shown to exacerbate RSB. The influence of alcohol use can further complicate these protective factors to influence RSB. Participants: 689 African American/Black and non-Hispanic White college students attending a public university in the Southeast United States. Method: This study sought to examine the relations between condom use self-efficacy and HIV knowledge with RSB and the moderating effect of alcohol use. Results: Findings showed positive associations between RSB and HIV knowledge and alcohol use. Unexpectedly, low frequency drinkers with high condom use self-efficacy were at increased risk for RSB compared to high frequency drinking counterparts. Conclusions: Findings point to the need to target prevention services for low-risk drinkers in college settings.