Several domestic and international trials of the use of preexposure prophylaxis (PrEP) for HIV prevention are ongoing among groups at high risk for HIV infection. The objective of this cross-sectional study was to assess self-perceived risk of HIV infection and attitudes about PrEP among 405 sexually transmitted disease (STD) clinic attendees in South Carolina. Self-percieved risk of HIV infection and attitudes about PrEP were assessed using three questions from a self-administered survey. Ordinal logistic regression and logistic regression were used to evaluate differences in risk perception for HIV infection and attitudes about the use of PrEP among risk groups. Compared to heterosexual participants, homosexual participants were significantly more likely to have knowledge of PrEP (odds ratio [OR]=6.7, 95% confidence interval [CI]: 1.70-26.1). Compared to those participants who had 1 sexual partner in the past 3 months, individuals who had 2 to 4 sexual partners in the past 3 months were approximately 2.35 times as likely to have a lower level of agreement with the statement "I believe I am at risk of getting HIV" (p=0.0003). Compared to female participants, respondents who were male were approximately 2.8 times as likely to have a lower level of agreement with the statement "If I had to it would be very difficult for me (or my partner) to both use condoms and take daily pills to prevent HIV infection" (p<0.0001). These results suggest the need for the creation of PrEP implementation programs that are tailored to self-perceived risk perception, age, and gender.