Appalachia Kentucky is recognized for increased cervical cancer incidence, morbidity and mortality and lower rates of Pap testing. Understanding the predictors of Human Papillomavirus (HPV) vaccine uptake is warranted among this population. The purpose of this exploratory research is to determine associations between HPV-related risk perceptions and uptake of free Gardasil offered to rural Appalachian women ages 18-26 attending regional health clinics. Young women (N = 247) were recruited from health clinics in Southeastern, Kentucky from March 2008 through September 2009. After completing a brief interview assessing seven HPV-related risk perceptions, women received a HPV vaccine voucher which provided the entire three-dose vaccine series free of charge. Whether women redeemed the voucher for dose one of Gardasil served as the study outcome variable. Hierarchical logistic regression was used to estimate the independent effects of each predictor variable on vaccine uptake. Less than 50% redeemed the voucher to receive dose one of the HPV vaccine. Five of the seven variables significantly predicted uptake. In a controlled analysis, only two predictors remained significant: "in general, vaccines are a good thing" (P = .02) and "I believe that getting the vaccine will be painful" (P = .03). The remaining three predictor variables (worry about having HPV [P = .07], HPV is serious enough for vaccination [P = .43], and not sure vaccine is safe [P = .22]) were not significant in the model. Health promotion programs designed for this population may enhance HPV vaccine uptake by creating more realistic perceptions about the inherent value of vaccines and by improving perceptions relative to injection pain.