The authors studied the characteristics of those who initiated the human papillomavirus (HPV) vaccine versus those who did not. Female members of Kaiser Permanente Southern California aged 9-26 years were identified and assessed for HPV vaccination between October 2006 and March 2008. Multivariable log-binomial regression was used to examine the association of the following factors with vaccine initiation: 1) demographics, 2) provider characteristics, 3) health care utilization, 4) women's health-related conditions, and 5) selected immune-related conditions. The study included 285,265 females. All analyses were stratified by 2 age groups: 9-17 years and 18-26 years. Black race (relative risk (RR)(9-17 years) = 0.93, RR(18-26 years) = 0.82), having a male primary care provider (RR(9-17 years) = 0.93, RR(18-26 years) = 0.84), and history of hospitalizations were associated with a lower likelihood of vaccine initiation. Higher neighborhood income level, physician office visits, and history of influenza vaccination (RR(9-17 years) = 1.20, RR(18-26 years) = 1.34) were associated with higher HPV vaccine uptake. Those with a history of sexually transmitted diseases were more likely and those with immune-related conditions were not less likely to initiate the HPV vaccine. These findings are helpful for interpreting the results of observational safety studies and providing insights for developing targeted HPV vaccination programs.