BACKGROUND Appalachia is a geographic region with high cervical cancer incidence and mortality rates, yet little is known about human papillomavirus (HPV) vaccination in this region. We determined HPV vaccine coverage among adolescent females from Appalachia, made comparisons to non-Appalachian females, and examined how coverage differs across subregions within Appalachia. METHODS We analyzed data from the National Immunization Survey-Teen 2008-2010 for adolescent females ages 13-17 (n = 1,951, Appalachian females and n = 25,468, non-Appalachian females). We examined HPV vaccine initiation (receipt of at least one dose), completion (receipt of at least three doses), and follow-through (completion among initiators). Analyses used weighted logistic regression. RESULTS HPV vaccine initiation [Appalachian = 40.8% vs. non-Appalachian = 43.6%; OR, 0.92; 95% confidence interval (CI), 0.79-1.07] and completion (Appalachian = 27.7% vs. non-Appalachian = 25.3%; OR, 1.12; 95% CI, 0.95-1.32) were similar between Appalachian and non-Appalachian females. HPV vaccine follow-through was higher among Appalachian females than non-Appalachian females (67.8% vs. 58.1%; OR, 1.36; 95% CI, 1.07-1.72). Vaccination outcomes tended to be higher in the Northern (completion and follow-through) and South Central (follow-through) subregions of Appalachia compared with non-Appalachian United States. Conversely, vaccination outcomes tended to be lower in the Central (initiation and completion) and Southern (initiation and completion) subregions. CONCLUSIONS In general, HPV vaccination in Appalachia is mostly similar to the rest of the United States. However, vaccination is lagging in regions of Appalachia where cervical cancer incidence and mortality rates are highest. CONCLUSIONS Current cervical cancer disparities could potentially worsen if HPV vaccine coverage is not improved in regions of Appalachia with low HPV vaccine coverage.