© 2016 Jacobs Institute of Women's Health. Background: Inadequate physician adherence to guidelines has received scant attention as a possible cause of suboptimal human papillomavirus (HPV) vaccination rates. We assessed the extent to which primary care physicians (PCPs) adhere to clinical guidelines and their reported intentions to prescribe HPV vaccine to females in the targeted age group, and how this is influenced by perceptions of guideline clarity and other factors. Methods: We surveyed 301 PCPs to explore their sociodemographic and practice-related characteristics, beliefs, professional norms, and perceived barriers to administer HPV vaccine. Logistic regression predicted the likelihood to prescribe HPV vaccine to 11- and 12-year-old girls on an array of variables hypothesized to influence physicians' recommendations. Results: Only 67% of PCPs reported being likely to prescribe HPV vaccine to 11- and 12-year-old patients. PCPs were more likely to prescribe vaccine to 11- and 12-year-old girls if they believed HPV vaccine guidelines were clear (odds ratio [OR], 1.85; 95% CI, 1.03-3.35), agreed with a mandate requirement (OR, 2.39; 95% CI, 1.01-5.61), felt comfortable discussing HPV vaccination with early adolescent girls (OR, 5.10; 95% CI, 2.75-9.45), and had at least 25% of their patients using public assistance to pay for their clinic visits (OR, 3.82; 95% CI, 1.91-7.34). Practice specialty (family physicians or pediatricians) and region were not significant predictors. Conclusions: PCPs exhibit moderate levels of adherence to professional guidelines regarding HPV vaccination. Potential public health benefits will not be realized without stronger efforts to improve the rates at which PCPs administer the vaccine, particularly to 11- and 12-year-olds for whom it is preferentially recommended.