Study Objective: We sought to evaluate knowledge of human papilloma virus (HPV) and attitudes toward the HPV vaccine among emergency department (ED) patients. Design: Cross-sectional survey. Setting: Three Boston EDs. Participants: We enrolled consecutive patients during two 24-hour periods at each site. Interventions: None. Main Outcome Measures: Knowledge of HPV and attitudes toward the HPV vaccine. Results: We enrolled 387 patients (81% of eligible). Overall, 242 (63%) participants had heard of HPV and 203 (52%) supported state-mandated vaccination. In the multivariate model, characteristics associated with lower awareness of HPV were: (1) older age (compared to age 18-26-years: OR 0.45 [95%CI, 0.20-0.99] for age 27-44 years, OR 0.26 [95%CI, 0.12-0.56] for age 45-64 years, and OR 0.10 [95%CI, 0.04-0.28] for age 65 year or older), (2) black race (compared to white: OR 0.31 [95%CI, 0.15-0.64]); and (3) lower annual household income (OR 0.39 [95%CI, 0.19-0.81] for $40,000 or less). Of those people who had heard of HPV, 82% knew of its relationship to cervical cancer, but only 61% thought it was a sexually transmitted disease (STD). Support for state-mandated vaccination was higher among participants who knew that HPV was an STD (OR 2.9 [95%CI 1.7-5.0]), but was not higher among those who had heard of HPV (OR 0.64 [95%CI 0.34-1.2]) or who knew that HPV causes cervical cancer (OR 0.85 [95%CI 0.45-1.6]). Conclusions: Support for state-mandated HPV vaccination appears to be driven more by the knowledge that HPV is an STD than by its role in cervical cancer. Awareness that HPV is transmitted through sexual activity does not decrease support for vaccination and may actually enhance it.