To assess HPV vaccine acceptability, focus groups of women (18–26 years), parents, community leaders, and healthcare providers were conducted throughout Ohio Appalachia. Themes that emerged among the 23 focus groups (n=114) about the HPV vaccine were: barriers (general health and vaccine specific), lack of knowledge (cervical cancer and HPV), cultural attitudes, and suggestions for educational materials and programs. Important Appalachian attitudes included strong family ties, privacy, conservative views, and lack of trust of outsiders to the region. There are differences in HPV vaccine acceptability among different types of community members highlighting the need for a range of HPV vaccine educational materials/programs to be developed that are inclusive of the Appalachian culture.