Objectives: The objective of this study was to determine factors that influence parent's acceptance of a mandatory school-based human papillomavirus (HPV) vaccination program.Methods: A convenience sample of 325 parents, with children aged 9 to 17 years old, completed a 53-item survey. Survey questions targeted their opinions about HPV, the HPV vaccine, and a mandatory HPV vaccination program.2 tests were used to examine relationships between survey items. Results: Characteristics of parents who believed the HPV vaccine should be mandated included limited financial resources (P ؍ .03), history of HPV-related disease (P ؍ .04), understanding their child's susceptibility (P ؍ .03), interest in HPV vaccination for their child (P ؍ .0001), and knowledge that the vaccine reduces the risk of cervical cancer (P ؍ .001). Parents of children aged 12 to 14 years old (P ؍ .02) or who knew the vaccine reduced their child's risk of developing genital warts (P ؍ .02) and cervical cancer (P ؍ .001) would be more likely to comply with a mandatory HPV vaccine program.Conclusions Although the quadrivalent human papillomavirus (HPV) vaccine has demonstrated robust efficacy and reasonable safety, suboptimal vaccination rates raise concern and questions.1-6 A survey conducted in 2007 by the Centers for Disease Control and Prevention found that approximately 25% of 13-to 17-year-old girls had received at least one dose of the HPV vaccine. 5 Moreover, far fewer 9-to 12-year-old and 18-to 26-year-old girls and women have initiated the vaccination series. The poor rate of HPV vaccine coverage for 9-to 12-year-old girls is particularly worrisome because this has been deemed the ideal age to vaccinate. 7 In comparison, coverage for school-entry vaccines during the 2007-2008 school year estimated by the Centers for Disease Control and Prevention varied between 94% (varicella) and 96% (hepatitis B).8 The differences in these vastly contrasting rates of vaccination are likely because of many factors, including cost, safety, knowledge, provider issues, access, and controversy.9 -11 However, one simple explanation is that school-entry vaccines are mandated and the HPV vaccine is not.Although discussion of mandating vaccines generates conflicting opinions, this approach has proven very beneficial from a public health perspective. School-mandated vaccination programs have increased coverage for other vaccines. [12][13][14][15] However, such an approach for the HPV vaccine has met some resistance by the medical community. 16 Further, only a minority of parents approve mandating the quadrivalent HPV vaccine. 17,18 Loss of parental autonomy, cost, insufficient data from clinical trials, and too This article was externally peer reviewed.