Objective To examine the association of knowledge about human papillomavirus (HPV) on the time to completion of the 3-dose quadrivalent vaccine series in an inner-city population of adolescent female subjects at high risk for infection. Study design We prospectively followed 139 female subjects aged 14-20 years enrolled in a vaccine surveillance study in New York City during a period of at least 24 months. Participants were given a 30-item true or false survey on HPV at enrollment and ranked according to the number of correct responses. Multivariate Cox regression was used to examine the association between level of knowledge about HPV and time to completion (in days) of vaccine dose 1-3, dose 1-2, and dose 2-3. Results Overall time to completion of the 3-dose vaccine ranged from 158 days to 1114 days. Participants in the high knowledge group (top quartile) were significantly more likely to complete the 3-dose series earlier (hazard ratio 1.69, 95% CI 1.03-2.77; P =.04), in particular doses 2-3 (hazard ratio 1.71, 95% CI 1.02-2.89; P =.04), than those with low-to-moderate knowledge (bottom 3 quartiles). Conclusions These findings suggest that knowledge of HPV is associated with shorter time to complete the 3-dose HPV vaccine series. Educational campaigns at time of vaccination may be important to improve vaccine adherence.