This study estimated county-level human papillomavirus (HPV) vaccination initiation rates in Alabama and determined whether disparities existed between counties in the Mississippi Delta region (MDR) and Appalachian region (AR).This study used an observational cross-sectional design.We used small area estimation methodology to estimate rates of medical provider-verified HPV vaccine initiation among school-age children in Alabama. Data for the study were retrieved from the 2015 National Immunization Survey (n = 22,205) and the US Census Bureau.The predictive model results showed that older age (odds ratio [OR] = 1.22, 95% confidence interval [CI] = 1.16, 1.29) was positively associated with vaccination initiation and black (OR = 0.79, 95% CI = 0.71, 0.87), white (OR = 0.56, 95% CI = 0.52, 0.60), and 'other' race/ethnicities (OR = 0.78, 95% CI = 0.70, 0.86), compared with Hispanics, and was negatively associated with vaccination initiation. The median (x̃)-modeled HPV vaccination initiation rate for all Alabama counties was 50.83% (interquartile range = 5.00%). Modeled HPV vaccination initiation rates were lowest in AR counties (x̃ = 49.81%), followed by counties not in the AR or MDR (x̃ = 53.26%) and MDR counties (x̃ = 54.90%).Culturally sensitive school-based HPV vaccine delivery programs are needed for children living in AR counties in Alabama.