Targeting human papillomavirus (HPV) vaccines to sub-populations most likely to benefit could be necessary if sufficient financing is not available for comprehensive immunization. Using data from 3276 sexually active young adult women in Wave III of the National Longitudinal Study of Adolescent Health, we investigated the feasibility of using behavioral risk factors to target sub-populations for HPV vaccination. We found associations between specific risk factors and vaccine-type-specific HPV infection (OR 1.7-2.1), and the likelihood of having HPV increased with increasing numbers of risk factors. However, no threshold number of risk factors predicted HPV infection with adequate specificity and sensitivity. Furthermore, at a population level, our analyses indicated that targeted approaches to HPV vaccination using specific risk factors were a poor strategy for vaccine implementation as they would exclude up to 80% of the otherwise eligible population from vaccination. Our results support implementation of comprehensive HPV vaccination strategies.