Objective: To assess knowledge of human papillomavirus (HPV) and perceived barriers to being vaccinated against the virus. Participants: Three hundred ninety-six undergraduate women enrolled at Penn State University in Fall 2008. Methods: A random sample of students were invited to participate in a Web-based survey. Results: Awareness of HPV and the vaccine was high, but knowledge of HPV-related facts averaged only 65% overall. Knowledge was significantly predicted by frequency of media exposure and physician encouragement to be vaccinated, but not by the number of sex partners nor the frequency of condom/dental dam use. On average, women indicated that 2 of the 10 barriers listed applied to them. Physician encouragement negatively predicted barriers at p = 0.066. No other predictors approached significance. Conclusions: Serious misconceptions remain about specific aspects of the diseases and how they are acquired. Health education efforts are needed to improve knowledge in college populations and counteract perceived barriers. (Contains 4 tables.)