BACKGROUND: Millions of women in the United States receive cervical screening in sexually transmitted disease (STD), family planning, and primary care clinical settings. OBJECTIVE: To inform current cervical screening programs. DESIGN: Measurement of abnormal Papanicolaou (Pap) tests and high-risk human papillomavirus (HPV) infection among demographically diverse women who received routine cervical screening from January 2003 to December 2005 in the United States. SETTING: 26 STD, family planning, and primary care clinics in 6 U.S. cities. PATIENTS: 9657 women age 14 to 65 years receiving routine cervical screening. MEASUREMENTS: Pap test results and high-risk HPV prevalence by Hybrid Capture 2 assay (Digene, Gaithersburg, Maryland). RESULTS: Among 9657 patients, overall high-risk HPV prevalence by Hybrid Capture 2 testing was 23% (95% CI, 22% to 24%). Prevalence was highest among women age 14 to 19 years (35% [CI, 32% to 38%]) and lowest among women age 50 to 65 years (6% [CI, 4% to 8%]). Prevalence by clinic type (adjusted for age and city) ranged from 26% (CI, 24% to 29%) in STD clinics to 17% (CI, 16% to 20%) in primary care clinics. Women younger than 30 years of age whose Pap test showed atypical squamous cells of undetermined significance had a high-risk HPV prevalence of 53%; women 30 years of age or older with normal Pap tests had a 9% prevalence. Values did not vary substantially by clinic type. LIMITATION: Hybrid Capture 2 and Pap testing were noncentralized, and consent was required for enrollment. CONCLUSION: High-risk HPV was widespread among women receiving cervical screening in the United States. Many women 30 years of age or older with normal Pap tests would need follow-up if Hybrid Capture 2 testing is added to cytology screening.