ABSTRACT: Anal cancer is caused by human papillomavirus (HPV), yet little is known about anal HPV infection among healthy young women.A total of 2017 sexually active women in the control arm of an HPV-16/18 vaccine trial had a single anal specimen collected by a clinician at the 4-year study visit. Samples were tested for HPV by SPF(10) PCR/DEIA/LiPA(25), version 1.A total of 4% of women had HPV-16, 22% had oncogenic HPV, and 31% had any HPV detected in an anal specimen. The prevalence of anal HPV was higher among women who reported anal intercourse, compared with those who did not (43.4% vs 28.4%; P< .001). Among women who reported anal intercourse, cervical HPV (adjusted odds ratio [aOR], 5.3 [95% confidence interval {CI}, 3.4-8.2]), number of sex partners (aOR, 2.2 [95% CI, 1.1-4.6] for ? 4 partners), and number of anal intercourse partners (aOR, 1.9 [95% CI, 1.1-3.3] for ? 2 partners) were independent risk factors for anal HPV detection. Among women who reported no anal intercourse, cervical HPV (aOR, 4.7 [95% CI, 3.7-5.9]), number of sex partners (aOR, 2.4 [95% CI, 1.7-3.4] for ? 4 partners), and report of anal fissures (aOR, 2.3 [95% CI, 1.1-4.8]) were associated with an increased odds of anal HPV detection.Anal HPV is common among young women, even those who report no anal sex, and was associated with cervical HPV infection. Anal fissures in women who report never having had anal intercourse may facilitate HPV exposure.NCT00128661.