Background: Uptake of human papillomavirus (HPV) vaccine remains low among adolescents in the United States. We sought to assess barriers to HPV vaccine provision in school health centers to inform subsequent interventions. Methods: We conducted structured interviews in the fall of 2010 with staff from all 33 school health centers in North Carolina that stocked HPV vaccine. Results: Centers had heterogeneous policies and procedures. Out-of-pocket costs for children and youth to receive privately purchased HPV vaccine were a key barrier to providing HPV vaccine within school health centers. Other barriers included students not returning consent forms, costs to clinics of ordering and stocking privately purchased HPV vaccine, and difficulty using the statewide immunization registry. Most (82%) school health centers were interested in hosting interventions to increase HPV vaccine uptake, especially those that the centers could implement themselves, but many had limited staff to support such efforts. Activities rated as more likely to raise HPV vaccine uptake were student incentives, parent reminders, and obtaining consent from parents while they are at school (all ps?<?0.05). Conclusions: Although school health centers reported facing several key barriers to providing HPV vaccine, many were interested in partnering with outside organizations on low-cost interventions to increase HPV vaccine uptake among adolescents.