Abstract Background: Human papillomavirus (HPV) vaccination could prevent most HPV-associated cancers, but few U.S. adolescents are vaccinated according to guidelines. To inform efforts to counsel parents more effectively, we sought to quantify their views on the best and worst reasons for guideline-consistent HPV vaccination. We hypothesized that parents' views would differ according to their vaccination confidence. Methods: We developed a best–worst scaling experiment to evaluate 11 reasons healthcare providers commonly give for HPV vaccination. The instrument was administered in 2016 via a national online survey to 1,177 parents of adolescents. Parents completed 11 choice tasks of 5 reasons each, indicating the best and worst reason in each task. We used conditional logistic regression to rank reasons for the sample overall and by vaccination confidence (low/high). Results: Parents viewed cancer prevention as the best reason for HPV vaccination (P < 0.001). Other commonly endorsed reasons were preventing a common infection, having lasting benefits, or being a safe vaccine (all P < 0.001). Reasons viewed as worst were: It is a scientific breakthrough; I got it for my own child; and your child is due (all P < 0.001). Stratified analyses indicated small differences in how often parents with low versus high vaccination confidence endorsed messages (P < 0.001), but the two groups ranked reasons similarly overall. Conclusions: Parents prioritized cancer prevention as the best reason for guideline-consistent HPV vaccination. Several other common reasons, including having vaccinated one's own child, may warrant additional testing. Impact: Providers should emphasize cancer prevention when discussing HPV vaccination, as recommended by the Centers for Disease Control and Prevention, the President's Cancer Panel, and others. Cancer Epidemiol Biomarkers Prev; 27(7); 762–7. ©2018 AACR.