Human papillomavirus (HPV) is the most prevalent sexually transmitted infection in the United States, affecting an estimated 79 million individuals.1 High-risk HPV types are associated with various cancers, with HPV types 16 and 18 causing an estimated two-thirds of all cervical cancers.1 Two vaccines (HPV4, Gardasil®; HPV2, Cervarix®) are now widely available for the primary prevention of HPV infection and cervical cancer.2 The Centers for Disease Control and Prevention (CDC) recommends routine HPV vaccination for females ages 11–12 and catch-up vaccination for females ages 13–26. Current CDC guidelines recommend that the second dose of the HPV vaccine series be administed 1–2 months after the first injection; the third dose is administered 6 months after the first dose.3 Unfortunately, HPV vaccination rates remain below Healthy People 2020 targets, especially among young adult women and in regions of the country that may need this cancer prevention strategy the most, including Appalachia.4–6 Lower HPV vaccination rates in Appalachia are problematic considering the higher prevalence of high-risk HPV infection and cervical cancer incidence and mortality rates in that region.7–11 Barriers to the initial uptake and eventual completion of the 3-dose HPV vaccine series among Appalachian women have been previously documented, with the high monetary cost of vaccination serving as a primary barrier.12–14 However, Crosby et al found that even when the barrier of cost was removed, young women residing in rural Appalachian Kentucky were less likely than their urban counterparts to accept and complete HPV vaccination.5 This finding suggests that factors unrelated to cost may serve as important barriers to HPV vaccination behaviors. Other noted barriers to HPV vaccination among Appalachian women include lack of transportation, limited parental/peer/health care provider support, cultural views, and lack of knowledge regarding cervical cancer prevention and HPV.13,15–17 There is an additional barrier to preventive cancer behavior, however, that has received limited attention as it relates to HPV vaccination, and that is the concept of fatalism. Fatalism has been examined as a potential determinant for engaging in preventive cancer strategies, including cancer information seeking, screening (eg, colorectal cancer screening, Papanicolaou [Pap] testing, mammography) and preventive behaviors (eg, diet, exercise, smoking).18–22 Although the definition of fatalism varies across studies and disciplines, the concept is often operationalized as mortality from cancer being inevitable and that the disease is beyond an individual’s personal control.19,23–25 Indeed, fatalistic beliefs have been previously identified as barriers to cancer prevention and screening among racial/ethnic minorities, individuals of lower socioeconomic status, the elderly, rural populations, and Appalachians.23,25–33 However, there has been limited research on the potential impact of fatalistic beliefs on HPV vaccination behaviors as a preventive cancer strategy, specifically among young Appalachian adults.13,34 Therefore, the purpose of this study was to examine whether fatalistic beliefs were associated with completion of the full HPV vaccine series among young women in Appalachian Kentucky.